Such ex vivo cell studies would make little sense, just like pure water can 100% kill all cancer cells. ... ...

Dennis,

if you have a specific study in mind, please give a reference.  But, in general I agree with Yicheng Ni.  Cultured cells can be killed or inhibited by a broad range of substances or growth conditions.  The validity and significance of any particular study that claims a beneficial treatment effect, must be evaluated based on the study design, the controls used, and the magnitude of the effect.

RW

I believe this is the source:linking increasing tomato consumption and decreasing risk of gastric cancer (inverse relationship).  What do you think?

Tomatoes, Tomato-Based Products, Lycopene, and Cancer ...

https://academic.oup.com/jnci/article/91/4/317/2543924/Tomatoes...

Inverse associations between tomato consumption and risk of gastric cancer were observed in all ... Sies H. Lycopene is more bioavailable from tomato paste than ...

Dennis

Dennis Mazur

Dennis,

• The paper you indicated is a review of epidemiological studies examining relationships between dietary habits in human subjects, especially with regard to tomato products, and cancer incidence for a range of different types of cancers including gastric cancer.  As far as I can see, there is no mention of cell culture studies and substances derived from tomatoes.  There is only one figure, Figure 1, shown at the end of the article that represents curves for 4 cell lines and phospholipid uptake, but this figure is not discussed in the paper nor is there a meaningful figure legend.  

Bob

Robert,

I will continue my search for the reference and get back to you.

Dennis

Dennis Mazur

Dennis, Robert, Yicheng:

A seminal paper here, and one I suspect Dennis Mazur may have had in mind, is the joint Korean-Agricultural Research Service (USDA) study of Mendel Friedman and colleagues [Friedman 2009] where multiple green and red tomato extracts were investigated, with high-tomatine tomato extracts strongly inhibiting several human cancer cell lines (breast (MCF-7), colon (HT-29), gastric (AGS), and hepatoma (liver) (HepG2)), confirming what numerous other studies have found, that the glycoalkaloids dehydrotomatine and α-tomatine are higly active anticancer components of tomato extracts, in part consequent to lowering biomarkers of oxidative stress and carcinogenesis, COX-2 suppression, and well-known immunostimulatory activity, these findings confirmed both in earlier studies [Choi 2012] [Friedman 2013] and in more recent studies [Yelken 2017] [Figueiredo-González M, Valentão P, Pereira DM, Andrade PB. Further insights on tomato plant: Cytotoxic and antioxidant activity of leaf extracts in human gastric cells. Food Chem Toxicol. 2017 Sep 09; 109(Pt 1):386-392.].

And on the human clinical front, we have from meta-analysis and systematic review of 42 studies (n=43, 851) [Rowles 2017] that higher levels of dietary and circulating concentrations of one such component, lycopene, are inversely associated with prostate cancer risk, with emergent data eagerly awaited from a dozen+ clinical trials in other malignancy types). And although we must await further randomized data to mature before drawing broader conclusions in the human clinical context, there appears no significant adverse signals for such consumption, and potential benefits in other domains of application such as cardiovascular disease.

REFERENCES

[Choi 2012] Choi SK, Ahn J-B, Kozukue N, et al. Structure–Activity Relationships of α-, β1-, γ-, and δ-Tomatine and Tomatidine against Human Breast (MDA-MB-231), Gastric (KATO-III), and Prostate (PC3) Cancer Cells. J Agric Food Chem 2012; 60(15):3891–3899.

[Figueiredo-González 2017] Figueiredo-González M, Valentão P, Pereira DM, Andrade PB. Further insights on tomato plant: Cytotoxic and antioxidant activity of leaf extracts in human gastric cells. Food Chem Toxicol. 2017 Sep 09; 109(Pt 1):386-392.

[Friedman 2009] Friedman M, Levin CE, Lee S-U, et al. Tomatine-Containing Green Tomato Extracts Inhibit Growth of Human Breast, Colon, Liver, and Stomach Cancer Cells. Agric Food Chem 2009; 57(13):5727–5733.

[Friedman 2013] Friedman M. Anticarcinogenic, cardioprotective, and other health benefits of tomato compounds lycopene, α-tomatine, and tomatidine in pure form and in fresh and processed tomatoes. J Agric Food Chem 2013 Oct 9; 61(40):9534-50.

[Rowles 2017] Rowles JL, Ranard KM, Smith JW, An R, Erdman JW. Increased dietary and circulating lycopene are associated with reduced prostate cancer risk: a systematic review and meta-analysis. Prostate Cancer Prostatic Dis. 2017 Apr 25

[Yelkin 2017] Yelken BÖ, Balcı T, Süslüer SY, eet al. The effect of tomatine on metastasis related matrix metalloproteinase (MMP) activities in breast cancer cell model. Gene. 2017 Sep 05; 627:408-411.

Constantine Kaniklidis

Director, Medical Research, No Surrender Breast Cancer Foundation (NSBCF)

Oncology Reviewer, Current Oncology [journal]

Society for Integrative Oncology (SIO)

European Association for Cancer Research (EACR)

As to the Friedman 2009 paper:

1.  Five cell lines were studied in the paper, 4 different types of cancer cell lines and 1 "normal liver" cell line (Chang cells).  It is indeed essential to compare the responses of tumor cell lines to normal cultured cell types in this type of study.  Unfortunately, Chang 'liver' cells obtained from ATCC (or probably anywhere else) are not liver cells, they are HeLa cells (see https://www.atcc.org/Products/All/CCL-13.aspx#characteristics for details).  Of course, HeLa cells are cervical tumor cells, they are not normal liver cells nor any other normal cell type.  As a result, this paper has no appropriate control with which to compare the responses of the known tumor cell types.  The toxicity or growth inhibition demonstrated may be completely non-specific for tumor cells.  The test substances may well be equally or more toxic to normal cells, a situation that would make them of no clinical interest.  There must be differential toxicity or inhibition for normal vs tumor cells.

2.  Even if we ignore that problem for the moment, the IC50 data for the cell studies have no error bars and there is no other indication of the 'n' for those experiments.  This could mean that these experiments were done only once or twice or that that results were so variable that the SD or SEM were very high, so the authors chose not include them.  Some type of error stats must be shown for readers to understand the strength or weakness of this type of data.

Unfortunately, this paper provides NO convincing evidence that tomato derived biological substances have any specific affect on the growth of or toxicity toward tumor cells of any type.

RW

https://www.atcc.org/Products/All/CCL-13.aspx#characteristics

Thanks Robert for your feedback and perspective. Note, I made no vouchsafe for the study, it was posited narrowly as possibly the one Dennis may have had in mind - or not.

Robert's objection about the contaminant status of the Chang cells is a valid, and welcome, one, but that is one cell line, and one study (for instance, we have: [Hwang 2006], inter al.). But we are I think all interested in the general issue of the anticancer potential of tomato extract components - not just in any one isolated study - including and especially tomatine and lycopene, in various tumor cell types, and in vivo [Wang, 2010] [Koul 2010] [Gupta, 2013a] [Gupta 2013b] [Gupta 2013c], and in the human context. And outside of this hepatic cell context, there  are numerous studies showing activity in mammary [Nahum 2001] [Alimohammadi 2017], prostate [Hwang 2005] [Talvas 2010] [Kolberg 2015] [Soares 2017], colon [Walfisch 2007] [Rudolf 2016] and many other cancer cell types, and across in vitro and in vivo data (and some provisional human data [Holzapfel 2013]).

I am for opening up the discussion, and I welcome hearing from Robert. and Dennis and  Yicheng, and others interested.

REFERENCES

[Alimohammadi 2017] Alimohammadi M, Lahiani MH1, McGehee D1, Khodakovskaya M. Polyphenolic extract of InsP 5-ptase expressing tomato plants reduce the proliferation of MCF-7 breast cancer cells. PLoS One. 2017 Apr 27; 12(4):e0175778.

[Gupta 2013a] Gupta P, Bansal MP, Koul A. Spectroscopic characterization of lycopene extract from Lycopersicum esculentum (Tomato) and its evaluation as a chemopreventive agent against experimental hepatocarcinogenesis in mice. Phytother Res 2013; 27:448–456.

[Gupta 2013b] Gupta P, Bansal MP, Koul A. Lycopene modulates initiation of N-nitrosodiethylamine induced hepatocarcinogenesis: Studies on chromosomal abnormalities, membrane fluidity and antioxidant defense system. Chem Biol Interact 2013, 206, 364–374.

[Gupta 2013c] Gupta P, Bansal MP, Koul A. Evaluating the effect of lycopene from Lycopersicum esculentum on apoptosis during NDEA induced hepatocarcinogenesis. Biochem. Biophys Res Commun 2013, 434, 479–485.

[Holzapfel 2013] Holzapfel NP, Holzapfel BM, Champ S, Feldthusen J, Clements J, Hutmacher DW. The potential role of lycopene for the prevention and therapy of prostate cancer: from molecular mechanisms to clinical evidence. Int J Mol Sci. 2013 Jul 12; 14(7):14620-46.

[Hwang 2005] Hwang ES, Bowen PE. Effects of tomato paste extracts on cell proliferation, cell-cycle arrest and apoptosis in LNCaP human prostate cancer cells. Biofactors. 2005; 23(2):75-84.

[Hwang 2006] Hwang ES, Lee HJ. Inhibitory effects of lycopene on the adhesion, invasion, and migration of SK-Hep1 human hepatoma cells. Exp Biol Med (Maywood) 2006 Mar; 231(3):322-7.

[Kolberg 2015] Kolberg M, Pedersen S, Bastani NE, Carlsen H, Blomhoff R, Paur I. Tomato paste alters NF-κB and cancer-related mRNA expression in prostate cancer cells, xenografts, and xenograft microenvironment. Nutr Cancer 2015; 67(2):305-15.

{Koul 2010] Koul A, Arora N, Tanwa L. Lycopene mediated modulation of 7,12-Dimethlybenz(α) anthracene induced hepatic clastogenicity in male Balb/c mice. Nutr Hosp 2010; 25:304–310.

[Nahum 2001] Nahum A, Hirsch K, Danilenko M, et al. Lycopene inhibition of cell cycle progression in breast and endometrial cancer cells is associated with reduction in cyclin D levels and retention of p27(Kip1) in the cyclin E-cdk2 complexes. Oncogene 2001 Jun 07; 20(26):3428-36.

[Rudolf 2016] Rudolf K, Rudolf E. Antiproliferative effects of α-tomatine are associated with different cell death modalities in human colon cancer cells. J Functional Foods 2016; 27:491-502.

[Soares 2017] Soares ND1, Machado CL, Trindade BB, et al. Lycopene Extracts from Different Tomato-Based Food Products Induce Apoptosis in Cultured Human Primary Prostate Cancer Cells and Regulate TP53, Bax and Bcl-2 Transcript Expression. Asian Pac J Cancer Prev. 2017 Feb 1; 18(2):339-345.

[Talvas 2010] Talvas J, Caris-Veyrat C, Guy L, et al. Differential effects of lycopene consumed in tomato paste and lycopene in the form of a purified extract on target genes of cancer prostatic cells. Am J Clin Nutr. 2010 Jun; 91(6):1716-24.

[Walfisch 2007] Walfisch S, Walfisch Y, Kirilov E, et al. Tomato lycopene extract supplementation decreases insulin-like growth factor-I levels in colon cancer patients. Eur J Cancer Prev. 2007 Aug;16(4):298-303.

[Wang 2010] Wang Y, Ausman LM, Greenberg AS, Russell RM, Wang XD. Dietary lycopene and tomato extract supplementations inhibit nonalcoholic steatohepatitis-promoted hepatocarcinogenesis in rats. Int J Cancer 2010; 126:1788–1796.

Constantine Kaniklidis

Director, Medical Research, No Surrender Breast Cancer Foundation (NSBCF)

Oncology Reviewer, Current Oncology [journal]

Society for Integrative Oncology (SIO)

European Association for Cancer Research (EACR)