Rajesh:
This is a vast topic, so I will only sketch a brief summary here:
As you noted, curcumin is a dietary spice and pigment derived from Curcuma longa (Turmeric) common in India and East Asia, with four major curcuminoids identified: curcumin, demethoxycurcumin, bis-demethoxycurcumin, and cyclocurcumin. The curcuminoids in curcumin exhibit a broad spectrum of anticancer, growth inhibitory, pro-apoptotic, chemopreventive, and anti-inflammatory properties, and have been shown, based on a truly vast body of robust research (thousands of studies in English journals alone), to be active in multiple cell signaling and molecular pathways [1-11]. These include:
cyclin D1 and cyclin E, c-myc, p21, p27, p53, HER-2, EGFR, AP-1, Bcl-2, Bcl-xL, Bax, cIAP1, xIAP, cFLIP, survivin, MMP-2/9 and adhesion molecules, VEGF, VEGFR1, IGF-1R, CXCR-4, NF-kB (as noted by my colleague Joachim, above), TNF, IL-6, IL-1, STAT3/5, JNK, COX-2, 5-LOX, iNOS, Wnt/beta-catenin, caspase activation pathways (caspase-8, 3, 9), death receptor pathways (DR4, DR5), mitochondrial pathways, and protein kinase pathway (JNK, PI3K/Akt, ERK, AMPK),
including both HDAC inhibitory activity [12], and significant anti-metastatic activity [13,14].
Activity ranges over several solid tumor types including breast cancer, hematological malignancies, and sarcomas. In addition, there are documented synergistic chemopreventive effects between curcuminoids and other natural dietary polyphenols (among them EGCG green tea polyphenols and soy-derived genistein), and traditional oncotherapeutic agents (among them 5-FU, gemcitabine, vinca alkaloids/vinorelbine, anthracyclines, and the HDAC inhibitor trichostatin A (TSA)), thus showing epigenetic activity.
Finally, recent evidence just reported from Danica Rowe and colleagues [15] at the Winship Cancer Institute and Emory University suggests that curcumin may be genotoxic (DNA-damaging), of particular benefit to triple negative and BRCA1 deficient patients, and this represents the first ever demonstration of the potential triple negative breast cancer (TNBC) specific activity of curcumin, showing curcumin-induced promotion of apoptosis and prevention of growth and migration of TNBC cells (the MDA-MB-468 (MDA468), HCC1937, and HCC1806 breast cancer lines). Curcumin induced DNA damage in triple negative breast cancer cells with observed promotion of apoptosis, and prevention of anchorage-independent growth and migration of triple negative breast cancer cells, and in addition with phosphorylation (on the ATM-and chk2-specific BRCA1 sites), increased expression, and cytoplasmic retention of the BRCA1 protein with prevents DNA repair, apparently independently of traditional IKK inhibition (but curcuminoids can also affect IKK inhibition, as noted again by my colleague Joachim, above). These seminal findings suggest curcumin's potential anticancer efficacy against substantial populations of difficult-to-treat TNBC patients, that is, those harboring tumors with wild-type brca1, which are downregulated in most sporadic TNBC cancer cells.
LOOKING FORWARD
New research has now established curcuminoid anticancer activity in the domains of cancer stem cells (CSCs) and microRNAs (miRNAs), and with positive human clinical trial data especially in prostate, pancreatic, colorectal cancer, and breast cancer. Finally, new and more powerful and bioavailable forms of curcumin are being explored including a polymer-encapsulated curcumin nanoparticle formulation (NanoCurc) for the treatment of brain tumor stem cells, as well as other new and emerging nanoparticle platforms including liposomes, micelles, nanoemulsions, and polymers, among many other exciting strategies on the frontier-edge of research.
REFERENCES
1. Sa G, Das T Anti cancer effects of curcumin: Cycle of life and death. Cell Div2008 Oct 3; 3(1):14.
2. Anand P, Sundaram C, Jhurani S, et al. Curcumin and cancer: An "old-age" disease with an "age-old" solution. Cancer Lett2008 May 5.
3. Prasada CP, Ratha G, Mathurc S, Bhatnagard D, Ralhan R. Potent growth suppressive activity of curcumin in human breast cancer cells: Modulation of Wnt/ß-catenin signaling. Chem Biol InterOctober 2009 181(2):263-271.
4. Grimaldo S, Tian F, Li LY Sensitization of endothelial cells to VEGI-induced apoptosis by inhibiting the NF-kappaB pathway. Apoptosis2009 May 6.
5. Yu S, Shen G, Khor TO, et al. Curcumin inhibits Akt/mammalian target of rapamycin signaling through protein phosphatase-dependent mechanism. [Journal Article] Mol Cancer Ther2008 Sep; 7(9):2609-20.
6. Sarkar FH, Li Y. Harnessing the fruits of nature for the development of multi-targeted cancer therapeutics. Cancer Treat Rev2009 Aug 4.
7. Lim HW, Lim HY, Wong KP. Uncoupling of oxidative phosphorylation by curcumin: implication of its cellular mechanism of action. Biochem Biophys Res Commun2009 Aug 25.
8. Amin ARMR, Kucuk O, Khuri FR, Shin DM. Perspectives for Cancer Prevention With Natural Compounds. J Clin OncolJune 1, 2009; 27(16):2712-2725.
9. Beevers CS, Chen L, Liu L, Luo Y, Webster NGJ, and Huang S. Curcumin Disrupts the Mammalian Target of Rapamycin-Raptor Complex. Cancer ResFebruary 1, 2009; 69(3):1000-1008.
10. Narasimhan M, Ammanamanchi S. Curcumin Blocks RON Tyrosine Kinase-Mediated Invasion of Breast Carcinoma Cells. Cancer ResJuly 1, 2008; 68(13):5185-5192.
11. Li M, Zhang Z, Hill DL, et al. Curcumin, a dietary component, has anticancer, chemosensitization, and radiosensitization effects by down-regulating the MDM2 oncogene through the PI3K/mTOR/ETS2 pathway.Cancer Res2007 Mar 1; 67(5):1988-96.
12. Chathoth S, Thayyullathil F, Galadari S. Curcumin Cell Signaling: A Possible Target for Chemotherapy. Curr Trends Biotechnol Pharm2008, 2(2):226-238.
13. Kuttan G, Kumar KB, Guruvayoorappan C, et al: Antitumor, anti-invasion, and antimetastatic effects of curcumin. Adv Exp Med Biol595:173–184, 2007.
14. Surh YJ, Chun KS: Cancer chemopreventive effects of curcumin. Adv Exp Med Biol595:149–172, 2007.
15. Rowe DL, Ozbay T, O’Regan RM, Nahta R. Modulation of the BRCA1 Protein and Induction of Apoptosis in Triple Negative Breast Cancer Cell Lines by the Polyphenolic Compound Curcumin. Breast Cancer: Basic Clin Res 2009:3 61-75.
Rajesh:
This is a vast topic, so I will only sketch a brief summary here:
As you noted, curcumin is a dietary spice and pigment derived from Curcuma longa (Turmeric) common in India and East Asia, with four major curcuminoids identified: curcumin, demethoxycurcumin, bis-demethoxycurcumin, and cyclocurcumin. The curcuminoids in curcumin exhibit a broad spectrum of anticancer, growth inhibitory, pro-apoptotic, chemopreventive, and anti-inflammatory properties, and have been shown, based on a truly vast body of robust research (thousands of studies in English journals alone), to be active in multiple cell signaling and molecular pathways [1-11]. These include:
cyclin D1 and cyclin E, c-myc, p21, p27, p53, HER-2, EGFR, AP-1, Bcl-2, Bcl-xL, Bax, cIAP1, xIAP, cFLIP, survivin, MMP-2/9 and adhesion molecules, VEGF, VEGFR1, IGF-1R, CXCR-4, NF-kB (as noted by my colleague Joachim, above), TNF, IL-6, IL-1, STAT3/5, JNK, COX-2, 5-LOX, iNOS, Wnt/beta-catenin, caspase activation pathways (caspase-8, 3, 9), death receptor pathways (DR4, DR5), mitochondrial pathways, and protein kinase pathway (JNK, PI3K/Akt, ERK, AMPK),
including both HDAC inhibitory activity [12], and significant anti-metastatic activity [13,14].
Activity ranges over several solid tumor types including breast cancer, hematological malignancies, and sarcomas. In addition, there are documented synergistic chemopreventive effects between curcuminoids and other natural dietary polyphenols (among them EGCG green tea polyphenols and soy-derived genistein), and traditional oncotherapeutic agents (among them 5-FU, gemcitabine, vinca alkaloids/vinorelbine, anthracyclines, and the HDAC inhibitor trichostatin A (TSA)), thus showing epigenetic activity.
Finally, recent evidence just reported from Danica Rowe and colleagues [15] at the Winship Cancer Institute and Emory University suggests that curcumin may be genotoxic (DNA-damaging), of particular benefit to triple negative and BRCA1 deficient patients, and this represents the first ever demonstration of the potential triple negative breast cancer (TNBC) specific activity of curcumin, showing curcumin-induced promotion of apoptosis and prevention of growth and migration of TNBC cells (the MDA-MB-468 (MDA468), HCC1937, and HCC1806 breast cancer lines). Curcumin induced DNA damage in triple negative breast cancer cells with observed promotion of apoptosis, and prevention of anchorage-independent growth and migration of triple negative breast cancer cells, and in addition with phosphorylation (on the ATM-and chk2-specific BRCA1 sites), increased expression, and cytoplasmic retention of the BRCA1 protein with prevents DNA repair, apparently independently of traditional IKK inhibition (but curcuminoids can also affect IKK inhibition, as noted again by my colleague Joachim, above). These seminal findings suggest curcumin's potential anticancer efficacy against substantial populations of difficult-to-treat TNBC patients, that is, those harboring tumors with wild-type brca1, which are downregulated in most sporadic TNBC cancer cells.
LOOKING FORWARD
New research has now established curcuminoid anticancer activity in the domains of cancer stem cells (CSCs) and microRNAs (miRNAs), and with positive human clinical trial data especially in prostate, pancreatic, colorectal cancer, and breast cancer. Finally, new and more powerful and bioavailable forms of curcumin are being explored including a polymer-encapsulated curcumin nanoparticle formulation (NanoCurc) for the treatment of brain tumor stem cells, as well as other new and emerging nanoparticle platforms including liposomes, micelles, nanoemulsions, and polymers, among many other exciting strategies on the frontier-edge of research.
REFERENCES
1. Sa G, Das T Anti cancer effects of curcumin: Cycle of life and death. Cell Div2008 Oct 3; 3(1):14.
2. Anand P, Sundaram C, Jhurani S, et al. Curcumin and cancer: An "old-age" disease with an "age-old" solution. Cancer Lett2008 May 5.
3. Prasada CP, Ratha G, Mathurc S, Bhatnagard D, Ralhan R. Potent growth suppressive activity of curcumin in human breast cancer cells: Modulation of Wnt/ß-catenin signaling. Chem Biol InterOctober 2009 181(2):263-271.
4. Grimaldo S, Tian F, Li LY Sensitization of endothelial cells to VEGI-induced apoptosis by inhibiting the NF-kappaB pathway. Apoptosis2009 May 6.
5. Yu S, Shen G, Khor TO, et al. Curcumin inhibits Akt/mammalian target of rapamycin signaling through protein phosphatase-dependent mechanism. [Journal Article] Mol Cancer Ther2008 Sep; 7(9):2609-20.
6. Sarkar FH, Li Y. Harnessing the fruits of nature for the development of multi-targeted cancer therapeutics. Cancer Treat Rev2009 Aug 4.
7. Lim HW, Lim HY, Wong KP. Uncoupling of oxidative phosphorylation by curcumin: implication of its cellular mechanism of action. Biochem Biophys Res Commun2009 Aug 25.
8. Amin ARMR, Kucuk O, Khuri FR, Shin DM. Perspectives for Cancer Prevention With Natural Compounds. J Clin OncolJune 1, 2009; 27(16):2712-2725.
9. Beevers CS, Chen L, Liu L, Luo Y, Webster NGJ, and Huang S. Curcumin Disrupts the Mammalian Target of Rapamycin-Raptor Complex. Cancer ResFebruary 1, 2009; 69(3):1000-1008.
10. Narasimhan M, Ammanamanchi S. Curcumin Blocks RON Tyrosine Kinase-Mediated Invasion of Breast Carcinoma Cells. Cancer ResJuly 1, 2008; 68(13):5185-5192.
11. Li M, Zhang Z, Hill DL, et al. Curcumin, a dietary component, has anticancer, chemosensitization, and radiosensitization effects by down-regulating the MDM2 oncogene through the PI3K/mTOR/ETS2 pathway.Cancer Res2007 Mar 1; 67(5):1988-96.
12. Chathoth S, Thayyullathil F, Galadari S. Curcumin Cell Signaling: A Possible Target for Chemotherapy. Curr Trends Biotechnol Pharm2008, 2(2):226-238.
13. Kuttan G, Kumar KB, Guruvayoorappan C, et al: Antitumor, anti-invasion, and antimetastatic effects of curcumin. Adv Exp Med Biol595:173–184, 2007.
14. Surh YJ, Chun KS: Cancer chemopreventive effects of curcumin. Adv Exp Med Biol595:149–172, 2007.
15. Rowe DL, Ozbay T, O’Regan RM, Nahta R. Modulation of the BRCA1 Protein and Induction of Apoptosis in Triple Negative Breast Cancer Cell Lines by the Polyphenolic Compound Curcumin. Breast Cancer: Basic Clin Res 2009:3 61-75.
I have to say I have not found a single study with a large number of patients that proves curcumin indeed helps prevent or alleviate cancer. Some Phase I/II studies, but no phase 3. I would be happy if someone can refer me to one.
As noted above, it is an inhibitor of inflammatory cytokines (e.g IL6, NFkB). It is therefore a potential useful tool in radioimmunotherapy - see: http://www.cell.com/trends/molecular-medicine/abstract/S1471-4914(13)00096-8. The problem in clinics is the poor bioavailability (scarce absorption, rapid elimination). In a clinical trial in Kyoto they are using a new form with better absorption in patients with pancreas or biliary tract cancer who failed standard chemotherapy. See: http://link.springer.com/article/10.1007%2Fs00280-013-2151-8
I add this on a positive effect of Curcumin on MGUS outcome, I remember about a noxious effect of Curcumin in Bile duct and Gallbladder Cancer incidence, that was accompanied in the regions of high Turmeric use of a decrease in the incidence of all types of dementia, but I was unable to retrieve references about thsi, and the articles found point to a beenficial effect of Curcumin on Galbladder diseases too
Am J Hematol. 2012 May;87(5):455-60. doi: 10.1002/ajh.23159. Epub 2012 Apr 4.
Monoclonal gammopathy of undetermined significance, smoldering multiple myeloma,
and curcumin: a randomized, double-blind placebo-controlled cross-over 4g study
and an open-label 8g extension study.
Golombick T, Diamond TH, Manoharan A, Ramakrishna R.
Author information:
Department of Endocrinology, St George Hospital, Sydney, Australia.
Comment in
Am J Hematol. 2012 May;87(5):453-4.
Am J Hematol. 2012 Oct;87(10):E80.
Am J Hematol. 2012 Oct;87(10):E80-1.
Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple
myeloma (SMM) represent useful models for studying multiple myeloma precursor
disease, and for developing early intervention strategies. Administering a 4g
dose of curcumin, we performed a randomised, double-blind placebo-controlled
cross-over study, followed by an open-label extension study using an 8g dose to
assess the effect of curcumin on FLC response and bone turnover in patients with
MGUS and SMM. 36 patients (19 MGUS and 17 SMM) were randomised into two groups:
one received 4g curcumin and the other 4g placebo, crossing over at 3 months. At
completion of the 4g arm, all patients were given the option of entering an
open-label, 8g dose extension study. Blood and urine samples were collected at
specified intervals for specific marker analyses. Group values are expressed as
mean ± 1 SD. Data from different time intervals within groups were compared using
Student's paired t-test. 25 patients completed the 4g cross-over study and 18 the
8g extension study. Curcumin therapy decreased the free light-chain ratio (rFLC),
reduced the difference between clonal and nonclonal light-chain (dFLC) and
involved free light-chain (iFLC). uDPYD, a marker of bone resorption, decreased
in the curcumin arm and increased on the placebo arm. Serum creatinine levels
tended to diminish on curcumin therapy. These findings suggest that curcumin
might have the potential to slow the disease process in patients with MGUS and
SMM.
Copyright © 2012 Wiley Periodicals, Inc.
PMID: 22473809 [PubMed - indexed for MEDLINE]
Ann Indian Acad Neurol. 2008 Jan;11(1):13-9. doi: 10.4103/0972-2327.40220.
The effect of curcumin (turmeric) on Alzheimer's disease: An overview.
Mishra S, Palanivelu K.
Author information:
Department of Neurology, VA/USC 16111, Sepulveda, CA, USA.
This paper discusses the effects of curcumin on patients with Alzheimer's disease
(AD). Curcumin (Turmeric), an ancient Indian herb used in curry powder, has been
extensively studied in modern medicine and Indian systems of medicine for the
treatment of various medical conditions, including cystic fibrosis, haemorrhoids,
gastric ulcer, colon cancer, breast cancer, atherosclerosis, liver diseases and
arthritis. It has been used in various types of treatments for dementia and
traumatic brain injury. Curcumin also has a potential role in the prevention and
treatment of AD. Curcumin as an antioxidant, anti-inflammatory and lipophilic
action improves the cognitive functions in patients with AD. A growing body of
evidence indicates that oxidative stress, free radicals, beta amyloid, cerebral
deregulation caused by bio-metal toxicity and abnormal inflammatory reactions
contribute to the key event in Alzheimer's disease pathology. Due to various
effects of curcumin, such as decreased Beta-amyloid plaques, delayed degradation
of neurons, metal-chelation, anti-inflammatory, antioxidant and decreased
microglia formation, the overall memory in patients with AD has improved. This
paper reviews the various mechanisms of actions of curcumin in AD and pathology.
PMCID: PMC2781139
PMID: 19966973 [PubMed]
Toxins (Basel). 2010 Apr;2(4):517-51. doi: 10.3390/toxins2040517. Epub 2010 Mar
31.
Phytochemicals in cancer prevention and therapy: truth or dare?
Russo M, Spagnuolo C, Tedesco I, Russo GL.
Author information:
Institute of Food Sciences, National Research Council, 83100, Avellino, Italy.
A voluminous literature suggests that an increase in consumption of fruit and
vegetables is a relatively easy and practical strategy to reduce significantly
the incidence of cancer. The beneficial effect is mostly associated with the
presence of phytochemicals in the diet. This review focuses on a group of them,
namely isothiocyanate, curcumin, genistein, epigallocatechin gallate, lycopene
and resveratrol, largely studied as chemopreventive agents and with potential
clinical applications. Cellular and animal studies suggest that these molecules
induce apoptosis and arrest cell growth by pleiotropic mechanisms. The anticancer
efficacy of these compounds may result from their use in monotherapy or in
association with chemotherapeutic drugs. This latter approach may represent a new
pharmacological strategy against several types of cancers. However, despite the
promising results from experimental studies, only a limited number of clinical
trials are ongoing to assess the therapeutic efficacy of these molecules.
Nevertheless, the preliminary results are promising and raise solid foundations
for future investigations.
PMCID: PMC3153217
PMID: 22069598 [PubMed - indexed for MEDLINE]
Cancer Chemother Pharmacol. 2011 Jul;68(1):157-64. doi:
10.1007/s00280-010-1470-2. Epub 2010 Sep 22.
A phase I/II study of gemcitabine-based chemotherapy plus curcumin for patients
with gemcitabine-resistant pancreatic cancer.
Kanai M, Yoshimura K, Asada M, Imaizumi A, Suzuki C, Matsumoto S, Nishimura T,
Mori Y, Masui T, Kawaguchi Y, Yanagihara K, Yazumi S, Chiba T, Guha S, Aggarwal
BB.
Author information:
Outpatient Oncology Unit, Kyoto University Hospital, 54 Shogoin-Kawahara-cho,
Sakyo-ku, Kyoto 606-8507, Japan. [email protected]
PURPOSE: Curcumin, a plant-derived natural polyphenol, could be a promising
anti-cancer drug and shows synergic effects with cytotoxic agents. We evaluated
the safety and feasibility of combination therapy using curcumin with
gemcitabine-based chemotherapy.
METHODS: Gemcitabine-resistant patients with pancreatic cancer received 8 g oral
curcumin daily in combination with gemcitabine-based chemotherapy. The primary
endpoint was safety for phase I and feasibility of oral curcumin for phase II
study.
RESULTS: Twenty-one patients were enrolled. No dose-limiting toxicities were
observed in the phase I study and oral curcumin 8 g/day was selected as the
recommended dose for the phase II study. No patients were withdrawn from this
study because of the intolerability of curcumin, which met the primary endpoint
of the phase II study, and the median compliance rate of oral curcumin was 100%
(Range 79-100%). Median survival time after initiation of curcumin was 161 days
(95% confidence interval 109-223 days) and 1-year survival rate was 19%
(4.4-41.4%). Plasma curcumin levels ranged from 29 to 412 ng/ml in five patients
tested.
CONCLUSIONS: Combination therapy using 8 g oral curcumin daily with
gemcitabine-based chemotherapy was safe and feasible in patients with pancreatic
cancer and warrants further investigation into its efficacy.
PMID: 20859741 [PubMed - indexed for MEDLINE]
Tumour Biol. 2013 Jul 26. [Epub ahead of print]
Curcumin inhibits lung cancer progression and metastasis through induction of
FOXO1.
Li ZC, Zhang LM, Wang HB, Ma JX, Sun JZ.
Author information:
Department of Ultrasound, The First Affiliated Hospital, General Hospital of
Chinese PLA, Beijing, 100048, China.
Recent population studies provide clues that the use of curcumin may be
associated with reduced incidence and improved prognosis of certain cancers. In
the present study, we demonstrated that curcumin acted as a growth inhibitor for
lung cancer cells. Our results found that curcumin inhibited cell proliferation,
which was associated with upregulation of the cyclin-dependent kinase inhibitors,
p27 and p21, and downregulation of cyclin D1. In addition, we showed that
curcumin induced the expression of forkhead box protein O1 (FOXO1) through
activation of extracellular signal-regulated kinase 1/2 signaling. These findings
provide evidence for a mechanism that may contribute to the antineoplastic
effects of curcumin and justify further work to explore potential roles for
activators of FOXO1 in the prevention and treatment of lung cancer.
PMID: 23888319 [PubMed - as supplied by publisher]
Rev Med Chir Soc Med Nat Iasi. 2012 Oct-Dec;116(4):1223-9.
Plant-derived anticancer agents - curcumin in cancer prevention and treatment.
Creţu E, Trifan A, Vasincu A, Miron A.
Author information:
University of Medicine and Pharmacy Grigore T Popa lasi, Faculty of Pharmacy.
Nowadays cancer is still a major public health issue. Despite all the progresses
made in cancer prevention, diagnosis and treatment, mortality by cancer is on the
second place after the one caused by cardiovascular diseases. The high mortality
and the increasing incidence of certain cancers (lung, prostate, colorectal)
justify a growing interest for the identification of new pharmacological agents
efficient in cancer prevention and treatment. In the last fifty years many
plant-derived agents (vinblastine, vincristine, vindesine, paclitaxel, docetaxel,
topotecan, irinotecan, elliptinium) played a major role in cancer treatment.
Other very promising plant-derived anticancer agents (combrestatins, betulinic
acid, roscovitine, purvalanols, indirubins) are in clinical or preclinical
trials. Curcumin, a liposoluble polyphenolic pigment isolated from the rhizomes
of Curcuma longa L. (Zingiberaceae), is another potential candidate for new
anticancer drug development. Curcumin has been reported to influence many
cell-signaling pathways involved in tumor initiation and proliferation. Curcumin
inhibits COX-2 activity, cyclin D1 and MMPs overexpresion, NF-kB, STAT and
TNF-alpha signaling pathways and regulates the expression of p53 tumor
suppressing gene. Curcumin is well-tolerated but has a reduced systemic
bioavailability. Polycurcumins (PCurc 8) and curcumin encapsulated in
biodegradable polymeric nanoparticles (NanoCurc) showed higher bioavailability
than curcumin together with a significant tumor growth inhibition in both in
vitro and in vivo studies. BILITY.
PMID: 23700916 [PubMed - indexed for MEDLINE]
1. World J Gastroenterol. 2013 Feb 21;19(7):984-93. doi: 10.3748/wjg.v19.i7.984.
Molecular mechanisms of chemopreventive phytochemicals against
gastroenterological cancer development.
Chung MY, Lim TG, Lee KW.
Author information:
Center for Food and Bioconvergence, Department of Agricultural Biotechnology,
Seoul National University, Seoul 151-742, South Korea.
Cancer is one of the leading causes of death worldwide. Commonly used cancer
treatments, including chemotherapy and radiation therapy, often have side effects
and a complete cure is sometimes impossible. Therefore, prevention, suppression,
and/or delaying the onset of the disease are important. The onset of
gastroenterological cancers is closely associated with an individual's lifestyle.
Thus, changing lifestyle, specifically the consumption of fruits and vegetables,
can help to protect against the development of gastroenterological cancers. In
particular, naturally occurring bioactive compounds, including curcumin,
resveratrol, isothiocyanates, (-)-epigallocatechin gallate and sulforaphane, are
regarded as promising chemopreventive agents. Hence, regular consumption of these
natural bioactive compounds found in foods can contribute to prevention,
suppression, and/or delay of gastroenterological cancer development. In this
review, we will summarize natural phytochemicals possessing potential antioxidant
and/or anti-inflammatory and anti-carcinogenic activities, which are exerted by
regulating or targeting specific molecules against gastroenterological cancers,
including esophageal, gastric and colon cancers.
PMCID: PMC3582010
PMID: 23467658 [PubMed - indexed for MEDLINE]
Int J Biochem Mol Biol. 2012;3(4):328-51. Epub 2012 Dec 24.
Cancer-linked targets modulated by curcumin.
Hasima N, Aggarwal BB.
Author information:
Cytokine Research Laboratory, Department of Experimental Therapeutics, The
University of Texas MD Anderson Cancer Center Houston, Texas, 77030, United
States ; Institute Science Biology, Faculty of Science, University of Malaya
50603 Kuala Lumpur, Malaysia.
In spite of major advances in oncology, the World Health Organization predicts
that cancer incidence will double within the next two decades. Although it is
well understood that cancer is a hyperproliferative disorder mediated through
dysregulation of multiple cell signaling pathways, most cancer drug development
remains focused on modulation of specific targets, mostly one at a time, with
agents referred to as "targeted therapies," "smart drugs," or "magic bullets."
How many cancer targets there are is not known, and how many targets must be
attacked to control cancer growth is not well understood. Although more than 90%
of cancer-linked deaths are due to metastasis of the tumor to vital organs, most
drug targeting is focused on killing the primary tumor. Besides lacking
specificity, the targeted drugs induce toxicity and side effects that sometimes
are greater problems than the disease itself. Furthermore, the cost of some of
these drugs is so high that most people cannot afford them. The present report
describes the potential anticancer properties of curcumin, a component of the
Indian spice turmeric (Curcuma longa), known for its safety and low cost.
Curcumin can selectively modulate multiple cell signaling pathways linked to
inflammation and to survival, growth, invasion, angiogenesis, and metastasis of
cancer cells. More clinical trials of curcumin are needed to prove its usefulness
in the cancer setting.
PMCID: PMC3533886
PMID: 23301199 [PubMed]
Cancer Lett. 1992 Sep 30;66(2):115-21.
Reversal of aflatoxin induced liver damage by turmeric and curcumin.
Soni KB, Rajan A, Kuttan R.
Author information:
Amala Cancer Research Centre, Trichur, Kerala State, India.
The effect of certain food additives on aflatoxin production by Aspergillus
parasiticus has been studied in vitro. Extracts of turmeric (Curcuma longa),
garlic (Allium sativum) and asafoetida (Ferula asafoetida) inhibited the
aflatoxin production considerably (more than 90%) at concentrations of 5-10
mg/ml. Similar results were also seen using butylated hydroxytoluene, butylated
hydroxyanisole and ellagic acid at concentration 0.1 mM. Curcumin, the
antioxidant principle from Curcuma longa did not have any effect on aflatoxin
production. Turmeric and curcumin were also found to reverse the aflatoxin
induced liver damage produced by feeding aflatoxin B1 (AFB1) (5 micrograms/day
per 14 days) to ducklings. Fatty changes, necrosis and biliary hyperplasia
produced by AFB1 were considerably reversed by these food additives.
PMID: 1394115 [PubMed - indexed for MEDLINE]
Planta Med. 1991 Feb;57(1):1-7.
Pharmacology of Curcuma longa.
Ammon HP, Wahl MA.
Author information:
Department of Pharmacology, Eberhard-Karls-Universität Tübingen, Federal Republic
of Germany.
The data reviewed indicate that extracts of Curcuma longa exhibit
anti-inflammatory activity after parenteral application in standard animal models
used for testing anti-inflammatory activity. It turned out that curcumin and the
volatile oil are at least in part responsible for this action. It appears that
when given orally, curcumin is far less active than after i.p. administration.
This may be due to poor absorption, as discussed. Data on histamine-induced
ulcers are controversial, and studies on the secretory activity (HCl, pepsinogen)
are still lacking. In vitro, curcumin exhibited antispasmodic activity. Since
there was a protective effect of extracts of Curcuma longa on the liver and a
stimulation of bile secretion in animals, Curcuma longa has been advocated for
use in liver disorders. Evidence for an effect on liver disease in humans is not
yet available. From the facts that after oral application only traces of curcumin
were found in the blood and that, on the other hand, most of the curcumin is
excreted via the faeces it may be concluded that curcumin is absorbed poorly by
the gastrointestinal tract and/or underlies presystemic transformation. Systemic
effects therefore seem to be questionable after oral application except that they
occur at very low concentrations of curcumin. This does not exclude a local
action in the gastrointestinal tract.
PMID: 2062949 [PubMed - indexed for MEDLINE]
Mol Cell Biochem. 2006 Aug;288(1-2):115-23. Epub 2006 May 12.
Curcumin combats against cigarette smoke and ethanol-induced lipid alterations in
rat lung and liver.
Vanisree AJ, Sudha N.
Author information:
Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600033,
Tamilnadu, India. [email protected]
BACKGROUND: Human population, in spite of the medical and scientific
achievements, still fall as a prey to the evils of habitual smoking and alcohol,
thus necessitating safer counteracting measures. Objective: To evaluate the
effect of cotreatment of curcumin (Curcuma longa) in rats subjected to acute
exposure to cigarette smoke (CS) and ethanol (EtOH).
METHODOLOGY: Of the four groups of experimental rats, a set of rats was subjected
to whole body exposure to cigarette smoke along with ethanol administration
serving as a model of CS+EtOH injury. Curcumin treatment was given to two sets of
rats: (i) one set receiving simultaneous CS+EtOH and (ii) one set of normal rats
without any administration. The other group of rats served as control. Blood,
liver and lung of rats were selected for assessment of CS+EtOH injury as well as
curcumin treatment.
RESULT: Altered lipid, lipoprotein profile and bile acid excretion were observed
in CS+EtOH rats along with premalignant pathological state in tissues. In treated
rats, the levels were maintained at near-normal levels along with near-normal
histology.
CONCLUSION: This biochemical picture on cotreatment with curcumin suggests that
curcumin could counteract the injurious effects of combined CS and EtOH and thus
might help to reduce the risk of hyperlipidemic disorders which develop due to
smoking and drinking.
PMID: 16691314 [PubMed - indexed for MEDLINE]
Asia Pac J Clin Nutr. 2002;11(4):314-8.
Effect of different curcumin dosages on human gall bladder.
Rasyid A, Rahman AR, Jaalam K, Lelo A.
Author information:
School of Medicine, University of North Sumatera, Medan, Indonesia.
Our previous study demonstrated that curcumin, an active compound of Curcuma
xanthorrhiza and C. domestica, produces a positive cholekinetic effect. A 20 mg
amount of curcumin is capable of contracting the gall bladder by up to 29% within
an observation time of 2 h. The aim of the current study was to define the dosage
of curcumin capable of producing a 50% contraction of the gall bladder, and to
determine if there is a linear relationship between doubling the curcumin dosage
and the doubling of gall bladder contraction. A randomised, single-blind,
three-phase, crossover-designed examination was carried out on 12 healthy
volunteers. Ultrasonography was carried out serially to measure the gall bladder
volume. The data obtained was analysed by analysis of variance (ANOVA). The
fasting volumes of gall bladders were similar (P > 0.50), with 17.28 +/- 5.47 mL
for 20 mg curcumin, 18.34 +/- 3.75 mL for 40 mg and 18.24 +/- 3.72 mL for 80 mg.
The percentage decrease in gall bladder volume 2 h after administration of 20, 40
and 80 mg was 34.10 +/- 10.16, 51.15 +/- 8.08 and 72.25 +/- 8.22, respectively,
which was significantly different (P < 0.01). On the basis of the present
findings, it appears that the dosage of cucumin capable of producing a 50%
contraction of the bladder was 40 mg. This study did not show any linear
relationship between doubling curcumin dosage and the doubling of gall bladder
contraction.
PMID: 12495265 [PubMed - indexed for MEDLINE]
A bit more
Cancer Lett. 2015 Aug 10;364(2):135-41. doi: 10.1016/j.canlet.2015.05.005. Epub
2015 May 12.
Curcumin inhibits cancer stem cell phenotypes in ex vivo models of colorectal
liver metastases, and is clinically safe and tolerable in combination with FOLFOX
chemotherapy.
James MI(1), Iwuji C(1), Irving G(1), Karmokar A(1), Higgins JA(1), Griffin-Teal
N(1), Thomas A(1), Greaves P(1), Cai H(1), Patel SR(1), Morgan B(1), Dennison
A(2), Metcalfe M(2), Garcea G(2), Lloyd DM(2), Berry DP(3), Steward WP(1),
Howells LM(4), Brown K(1).
Author information:
(1)Department of Cancer Studies, University of Leicester, Leicester Royal
Infirmary, Leicester, LE2 7LX, UK. (2)Department of Hepatobiliary Surgery,
Leicester General Hospital, Gwendolen Road, Leicester, UK. (3)Department of
Hepatobiliary Surgery, University Hospitals of Wales, Cardiff, UK. (4)Department
of Cancer Studies, University of Leicester, Leicester Royal Infirmary, Leicester,
LE2 7LX, UK. Electronic address: [email protected].
In vitro and pre-clinical studies have suggested that addition of the
diet-derived agent curcumin may provide a suitable adjunct to enhance efficacy of
chemotherapy in models of colorectal cancer. However, the majority of evidence
for this currently derives from established cell lines. Here, we utilised
patient-derived colorectal liver metastases (CRLM) to assess whether curcumin may
provide added benefit over 5-fluorouracil (5-FU) and oxaliplatin (FOLFOX) in
cancer stem cell (CSC) models. Combination of curcumin with FOLFOX chemotherapy
was then assessed clinically in a phase I dose escalation study. Curcumin alone
and in combination significantly reduced spheroid number in CRLM CSC models, and
decreased the number of cells with high aldehyde dehydrogenase activity
(ALDH(high)/CD133(-)). Addition of curcumin to oxaliplatin/5-FU enhanced
anti-proliferative and pro-apoptotic effects in a proportion of patient-derived
explants, whilst reducing expression of stem cell-associated markers ALDH and
CD133. The phase I dose escalation study revealed curcumin to be a safe and
tolerable adjunct to FOLFOX chemotherapy in patients with CRLM (n = 12) at doses
up to 2 grams daily. Curcumin may provide added benefit in subsets of patients
when administered with FOLFOX, and is a well-tolerated chemotherapy adjunct.
Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights
reserved. PMID 25979230
Daru. 2015 Jun 12;23(1):33. [Epub ahead of print]
Curcumin as a double-edged sword for stem cells: dose, time and cell
type-specific responses to curcumin.
Attari F(1,)(2), Zahmatkesh M(3), Aligholi H(4,)(5), Mehr SE(6), Sharifzadeh
M(7), Gorji A(8,)(9), Mokhtari T(10), Khaksarian M(11), Hassanzadeh G(12,)(13).
Author information:
(1)Department of Neuroscience, School of Advanced Technologies in medicine,
Tehran University of Medical Sciences, Tehran, Iran. [email protected].
(2)Shefa Neuroscience Research Center, Khatamolanbia Hospital, Tehran, Iran.
[email protected]. (3)Department of Neuroscience, School of Advanced
Technologies in medicine, Tehran University of Medical Sciences, Tehran, Iran.
[email protected]. (4)Department of Neuroscience, School of Advanced
Technologies in medicine, Tehran University of Medical Sciences, Tehran, Iran.
[email protected]. (5)Shefa Neuroscience Research Center, Khatamolanbia
Hospital, Tehran, Iran. [email protected]. (6)Department of Pharmacology,
School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
[email protected]. (7)Faculty of Pharmacy, and Pharmaceutical Sciences Research
Center, Tehran University of Medical Sciences, Tehran, Iran.
[email protected]. (8)Shefa Neuroscience Research Center, Khatamolanbia
Hospital, Tehran, Iran. [email protected]. (9)Epilepsy Research Center,
WestfälischeWilhelms-UniversitätMünster, Münster, Germany.
[email protected]. (10)Department of Anatomy, School of Medicine, Tehran
University of Medical Sciences, Tehran, Iran. [email protected].
(11)Department of Physiology, Medical College, Lorestan University of Medical
Sciences, Khorramabad, Iran. [email protected]. (12)Department of
Neuroscience, School of Advanced Technologies in medicine, Tehran University of
Medical Sciences, Tehran, Iran. [email protected]. (13)Department of
Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
BACKGROUND: The beneficial effects of curcumin which includes its antioxidant,
anti-inflammatory and cancer chemo-preventive properties have been identified.
Little information is available regarding the optimal dose and treatment periods
of curcumin on the proliferation rate of different sources of stem cells.
METHODS: In this study, the effect of various concentrations of curcumin on the
survival and proliferation of two types of outstanding stem cells which includes
bone marrow stem cells (BMSCs) and adult rat neural stem/progenitor cells
(NS/PCs) at different time points was investigated. BMSCs were isolated from
bilateral femora and tibias of adult Wistar rats. NS/PCs were obtained from
subventricular zone of adult Wistar rat brain. The curcumin (0.1, 0.5, 1, 5 and
10 μM/L) was added into a culture medium for 48 or 72 h. Fluorescent density of
5-bromo-2'-deoxyuridine (Brdu)-positive cells was considered as proliferation
index. In addition, cell viability was assessed by MTT assay.
RESULTS: Treatment of BMSCs with curcumin after 48 h, increased cell survival and
proliferation in a dose-dependent manner. However, it had no effect on NSCs
proliferation except a toxic effect in the concentration of 10 μM of curcumin.
After a 72 h treatment period, BMSCs and NS/PCs survived and proliferated with
low doses of curcumin. However, high doses of curcumin administered for 72 h
showed toxic effects on both stem cells.
CONCLUSIONS: These findings suggest that curcumin survival and proliferative
effects depend on its concentration, treatment period and the type of stem cells.
Appropriate application of these results may be helpful in the outcome of
combination therapy of stem cells and curcumin.
PMID: 26063234 [PubMed - as supplied by publisher]
D: 25979230 [PubMed - in process]
J Anim Sci. 2015 Apr;93(4):1656-65. doi: 10.2527/jas.2014-8244.
Dietary curcumin supplementation protects against heat-stress-impaired growth
performance of broilers possibly through a mitochondrial pathway.
Zhang JF, Hu ZP, Lu CH, Yang MX, Zhang LL, Wang T.
A total of 400 1-d-old Arbor Acres broiler chicks were raised at a recommended
environmental temperature from d 1 to 20 (experimental day [ED] = ED to ED). On
ED, the chicks were weighed and reallocated into 5 treatment groups, with 8
replicates of 10 birds each. The 5 treatment groups were as follows: the control
group, in which chicks were housed at 22 ± 1°C and fed the basal diet, and the
HS, HS-CUR50, HS-CUR100, and HS-CUR200 groups, in which chicks were housed at 34
± 1°C for 8 h (0900-1700 h) and 22 ± 1°C for the rest time and fed the basal diet
with 0, 50, 100, and 200 mg/kg curcumin, respectively. From ED to ED, the heat
treatment lasted for 20 consecutive days. The results showed that heat-stressed
broilers had greater ( < 0.05) average head surface and rectal temperature on ED
and ED than the non-heat-stressed broilers. Diets supplied with 50 and 100 mg/kg
curcumin increased ( < 0.05) the G:F compared to the heat-stressed groups.
Mitochondrial malondialdehyde levels, an index of lipid peroxidation, in the
breast muscle were 15.15 and 9.09% higher ( < 0.05) in 50 and 100 mg/kg curcumin
supplemented groups than that of the heat-stressed group, respectively. Curcumin
supplementation (50, 100, and 200 mg/kg) increased ( < 0.05) mitochondrial
glutathione content and glutathione peroxidase, glutathione S-transferase, and
manganese superoxide dismutase activities compared to heat-stressed broilers.
Curcumin supplementation (50, 100, and 200 mg/kg) resulted in a decrease (
Turmeric is a spice that is often used as a food flavouring in Asian dishes. It belongs to the ginger family. It is also known as Indian saffron, jiang huang, haridra, haldi, as the major ingredient of curry powder 2, and as a bright yellow orange food colouring agent (E100).
Turmeric grows in many Asian countries such as India. It has been used for many years in some herbal remedies. The main active ingredient is curcumin or diferuloyl methane.
Currently there is no research evidence to show that turmeric or curcumin can prevent or treat cancer but early trials have shown some promising results.
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Research into preventing cancer
A phase I clinical trial looked at giving curcumin to 25 patients with pre cancerous changes in different organs. This study seemed to show that curcumin could stop the precancerous changes becoming cancer.
Research has also shown that there are low rates of certain types of cancer in countries where people eat curcumin at levels of about 100 to 200 mg a day over long periods of time.
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Research into treating cancer
A number of laboratory studies on cancer cells have shown that curcumin does have anticancer effects. It seems to be able to kill cancer cells and prevent more from growing. It has the best effects on breast cancer, bowel cancer, stomach cancer and skin cancer cells.
A 2007 American study that combined curcumin with chemotherapy to treat bowel cancer cells in a laboratory showed that the combined treatment killed more cancer cells than the chemotherapy alone.
A 2007 American study in mice seemed to show that curcumin helped to stop the spread of breast cancer cells to other parts of the body.
Doctors think that curcumin stays in the digestive system and is absorbed by the cells in the bowel. To find out more, a small study in the UK looked at how curcumin is absorbed from the human gut into liver cells. This study looked at how much of the curcumin is absorbed into both cancer cells and normal cells. This was a very small study of people with bowel cancer that had spread to the liver. They were given curcumin for 7 days before surgery.
During the surgery doctors removed liver tissue and they then then measured the levels of curcumin in the tissue. The results showed that the level of curcumin absorbed into the liver was not high enough to have any anticancer effect. The researchers suggested that future clinical trials of curcumin should focus on preventing bowel tumours. Several studies have shown that curcumin taken as capsules does get absorbed by the gut and is present in the blood. But the amount in the blood is small.For more plz read at following links
http://www.cancerresearchuk.org/about-cancer/cancers-in-general/cancer-questions/can-turmeric-prevent-bowel-cancer
http://www.anticancerbook.com/post/Turmeric-and-black-pepper-fight-cancer-stem-cells.html
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