Metformin and Cancer STEM cells.

Dr. Weeks’ Comment:  I applaud the authors of this article demonstrating that the common oral diabetes drug Metformin  “targets CSCs in breast cancer, pancreatic cancer, glioblastoma and colon cancer”.  It does so by lowering circulating blood sugar but also by disrupting oxidative phosphorylation and reducing ATP production at the level of the mitochondria. This creates an energy crisis for the cancer process. So this is a cheap and relatively safe remedy for cancer STEM cells. One I have recommended for almost a decade now.

But I object to this unscientific statement that “advanced prostate cancer is more difficult to treat and if metastatic, is incurable.”  Incurable?  That statement defies true scientific assessment. No null hypothesis can be tested. It is therefore either a non-scientific statement squatting in the middle of a peer-reviewed scientific article or it is a statement of a non-scientist. So all you people with prostate cancer out there, discount that “care- less”, throw away unscientific comment and recall what one of the great doctors in history Paracelsus taught: “There are no incurable illness. There are just incurable people.”    Also, send a penny and read the classic survival text for cancer patients Love Medicine and Miracles by Dr. Bernie Siegel MD – Yale Cancer Surgeon turned inspired healer.   Finally, it would have been nice for the author to point out the common herbal remedy Berberine is equally as beneficial as Metformin – and cheaper. 


Prostate Cancer and Prostatic Diseases 18, 303-309 (December 2015) | doi:10.1038/pcan.2015.35

Metformin and prostate cancer stem cells: a novel therapeutic target

M J MayerL H Klotz and V Venkateswaran

Prostate cancer is the second most frequently diagnosed cancer in the world. Localized disease can be effectively treated with radiation therapy or radical prostatectomy. However, advanced prostate cancer is more difficult to treat and if metastatic, is incurable. There is a need for more effective therapy for advanced prostate cancer. One potential target is the cancer stem cell (CSC). CSCs have been described in several solid tumors, including prostate cancer, and contribute to therapeutic resistance and tumor recurrence. Metformin, a common oral biguanide used to treat type 2 diabetes, has been demonstrated to have anti-neoplastic effects. Specifically, metformin targets CSCs in breast cancer, pancreatic cancer, glioblastoma and colon cancer. Metformin acts directly on the mitochondria to inhibit oxidative phosphorylation and reduce mitochondrial ATP production. This forces tumor cells to compensate by increasing the rate of glycolysis. CSCs rely heavily on mitochondrial oxidative phosphorylation for energy production. The glycolytic switch results in an energy crisis in these cells. Metformin could be used to exploit this metabolic weakness in CSCs. This would increase CSC sensitivity to conventional cancer therapies, circumventing treatment resistance and enhancing treatment efficacy. This review will explore the characteristics of prostate CSCs, their role in tumor propagation and therapeutic resistance and the role of metformin as a potential prostate CSC sensitizer to current anticancer therapies.


Metformin inhibits the inflammatory response associated with cellular transformation and cancer stem cell growth


Metformin, the first-line drug for treating diabetes, inhibits cellular transformation and selectively kills cancer stem cells in breast cancer cell lines. In a Src-inducible model of cellular transformation, metformin inhibits the earliest known step in the process, activation of the inflammatory transcription factor NF-κB. Metformin strongly delays cellular transformation in a manner similar to that occurring upon a weaker inflammatory stimulus. Conversely, inhibition of transformation does not occur if metformin is added after the initial inflammatory stimulus. The antitransformation effect of metformin can be bypassed by overexpression of Lin28B or IL1β, downstream targets of NF-κB. Metformin preferentially inhibits nuclear translocation of NF-κB and phosphorylation of STAT3 in cancer stem cells compared with non-stem cancer cells in the same population. The ability of metformin to block tumor growth and prolong remission in xenografts in combination with doxorubicin is associated with decreased function of the inflammatory feedback loop. Lastly, metformin-based combinatorial therapy is effective in xenografts involving inflammatory prostate and melanoma cell lines, whereas it is ineffective in noninflammatory cell lines from these lineages. Taken together, our observations suggest that metformin inhibits a signal transduction pathway that results in an inflammatory response. As metformin alters energy metabolism in diabetics, we speculate that metformin may block a metabolic stress response that stimulates the inflammatory pathway associated with a wide variety of cancers.

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