Dear Authors of this interesting Project,
Just this Project touches with some my published works, the main of which I must present two works:
1) Ponizovskiy M.R., (2013), Biophysical and biochemical transmutation of mitochondrial function in cancer genesis, Biochemistry & Analytical Biochemistry, Volume 2, Issue 3, 1 – 9, doi:10.4172/2161-1009.1000137.
2) Ponisovskiy M.R., (2010), “Cancer metabolism and the Warburg effect as anabolic process outcomes of oncogene operation”, Critical Reviews in Eukaryotic Gene Expression, 20 (4), 325 – 339.
Therefore I accept your Project entirely and have only one query: Whether did you consider the main role of anabolic endergonic processes in oncogenesis of G1/S phases cellular cycle causing irrepressible cancer tumor growth etc.besides catabolic exerginic processes in mitochondria? [Please, see the works above]
This has been a decades long project. We have determined that SOD2 is a fundamental redox enzyme, not just an "antioxidant".
We fist proposed a biological role in:
Oberley LW, Buettner GR. (1979) The role of superoxide dismutase in cancer: A review. Cancer Research 39: 1141-1149. **Citation Classic** (> 100 citations) PMID: 217531 http://cancerres.aacrjournals.org/cgi/content/abstract/39/4/1141
Oberley LW, Oberley TD, Buettner GR. (1981) Cell division in normal and transformed cells: The possible role of superoxide dismutase and hydrogen peroxide. Med. Hypotheses 7: 21-42. PMID: 6259499 http://dx.doi.org/doi:10.1016/0306-9877(81)90018-9
My colleague, the late Larry Oberley, has many publications addressing SOD2 and its biology. As one example, see:
Venkataraman S, Jiang X, Weydert CJ, Zhang Y, Zhang HJ, Goswami PC, Ritchie JM, Oberley LW, Buettner GR. (2005) Manganese superoxide dismutase overexpression inhibits the growth of androgen-independent prostate cancer cells. Oncogene. 24:77-89. PMID: 15543233 http://dx.doi.org/doi:10.1038/sj.onc.1208145
Most researchers have misconceptions on the biochemistry of SOD2, see:
Buettner GR, Ng CF, Wang M, Rodgers VGJ, Schafer FQ. (2006) A new paradigm: Manganese superoxide dismutase influences the production of H2O2 in cells and thereby their biological state. Free Radic Biol Med. 41:1338-1350. PMID: 17015180 http://dx.doi.org/10.1016/j.freeradbiomed.2006.07.015 PMCID: PMC2443724
Increased activity of SOD2, of course, lowers the the steady-state concentration of superoxide, but actually increases its flux and then naturally the flux of H2O2 increases.
Buettner GR. (2011) Superoxide dismutase in redox biology: The roles of superoxide and hydrogen peroxide. Anticancer Agents Med Chem. 11:341-346. PMID: 21453242 http://dx.doi.org/10.2174/187152011795677544 PMCID: PMC3131414
The challenge is translating these findings to the clinic. We are doing this via P-AscH- , i.e. high dose, IV ascorbate.
Welsh JL, Wagner BA, van ’t Erve TJ, Zehr PS, Berg DJ, Halfdanarson TR, Yee NS, Bodeker KL, Du J, Roberts LJ 2nd, Levine M, Buettner GR, Cullen JJ. (2013) Pharmacological ascorbate with gemcitabine for the control of metastatic and node-positive pancreatic cancer (PACMAN): Results from a phase I clinical trial. Cancer Chemotherapy and Pharmacology. 71(3):765-775. PMID: 23381814 http://dx.doi.org/10.1007/s00280-013-2070-8 PMCID: PMC3587047
Schoenfeld JD, Sibenaller ZA, Mapuskar KA, Wagner BA, Cramer-Morales KL, Furqan M, Sandhu S, Carlisle TL, Smith MC, Abu Hejleh T, Berg DJ, Zhang J, Keech J, Parekh KR, Bhatia S, Monga V, Bodeker KL, Ahmann L, Vollstedt S, Brown H, Shanahan Kauffman EP, Schall ME, Hohl RJ, Clamon GH, Greenlee JD, Howard MA, Shultz MK, Smith BJ, Riley DP, Domann FE, Cullen JJ, Buettner GR, Buatti JM, Spitz DR, Allen BG. (2017) O2·- and H2O2-mediated disruption of Fe metabolism causes the differential susceptibility of NSCLC and GBM cancer cells to pharmacological ascorbate. Cancer Cell. 31(4):487-500.e8 PMID: 28366679 http://dx.doi.org/10.1016/j.ccell.2017.02.018 PMCID: PMC5497844
Our success relies on quantiation:
Buettner GR, Wagner BA, Rodgers VGJ. (2013) Quantitative Redox Biology: An approach to understanding the role of reactive species in defining the cellular redox environment. Cell Biochemistry and Biophysics. 67:477-483. PMID: 22161621 http://dx.doi.org/10.1007/s12013-011-9320-3 PMCID: PMC3661692
Doskey CM, van ‘t Erve TJ, Wagner BA, Buettner GR. (2015) Moles of a substance per cell is a highly informative dosing metric in cell culture. PLoS ONE 10(7): e0132572. PMID: 26172833 http://dx.doi.org/doi:10.1371/journal.pone.0132572 Open Access PMCID: PMC4501792
Buettner GR. (2015) Moving free radical and redox biology ahead in the next decade(s). Free Radic Biol Med. 78:236-238. PMID: 25450329 http://dx.doi.org/10.1016/j.freeradbiomed.2014.10.578 PMCID: PMC4331124
Doskey CM, Buranasudja V, Wagner BA, Wilkes JG, Du J, Cullen JJ, Buettner GR. (2016) Tumor cells have decreased ability to metabolize H2O2: Implications for pharmacological ascorbate in cancer therapy. Redox Biology. 10:274-284. PMID: 27833040 http://dx.doi.org/10.1016/j.redox.2016.10.010 Open Access PMCID: PMC5106370
These are some examples.
Thank you for your interest.
Garry Buettner
- Badges
- Science topic
- Similar topics
- Chemistry
- Pharmacology
- Medical Pharmacology
- Clinical Pharmacology