Cancer Therapy Synergy: PDT with Metformin

Metformin is an inexpensive, well-tolerated drug that is commonly used for the first-line treatment of type 2 diabetes.  In recent years, this oral agent has emerged as a potential tool for improving the treatment outcomes for many common cancers.  It has been estimated that metformin may contribute to an estimated 30% reduction in the lifetime risk of cancer for people with diabetes.

Metformin may impact the metabolism of the host in a variety of ways that could ultimately block the growth and progression of cancer. Scientists at the University of Medicine and Pharmacy in Cluj-Napoca, Romania, recently sought to assess the effect of the combined treatment of Metformin with photodynamic therapy (PDT).  They found that the combination of metformin with PDT led to a reduction in markers of inflammation as well as increased killing of tumor cells.  Part of this killing was due to the process known as necrosis, which is also more conducive to improved anti-cancer immunity.

The combined therapy also led to a significant drop in the activity of MMP-2, an enzyme linked with the metatastic spread of cancer.  Taken together, these findings may indicate that PDT-metformin combination might prove to be a promising new cancer treatment strategy, as reported in the September 2014 Journal of Photochemistry and Photobiology.

The human body contains a natural photosensitizer called protoporphyrin IX.  The generation of this compound is enhanced by another natural compound, 5-aminolevulinic acid (5-ALA).  The latter compound has long been one of the mainstays of the photodynamic approach.  Simply put, 5-ALA is administered either orally or topically, and this leads to the light-sensitizing effect that destroys diseased or abnormal cells, including cancer cells.

It was recently shown that 5-ALA lowers blood sugar levels during fasting and after glucose loading in people with prediabetes.  In a series of animal experiments, researchers at the Kyoto Prefectural University in Kyoto, Japan, showed that 5-ALA lessened glucose intolerance and also improved various measures of metabolic health (hypertriglyceridemia, hyperleptinemia, and mitochondrial dysfunction).

The Kyoto findings suggest that 5-ALA reduces diabetic abnormalities through favorable effects on fat metabolism and mitochondrial funcitioning, as reported in the June 2014 issue of Nutrition Research.  Whether these effects will translate to human beings remains to be demonstrated in clinical trials.

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Nenu I, Popescu T, Aldea MD, Craciun L, Olteanu D, Tatomir C, Bolfa P, Ion RM, Muresan A, Filip AG. Metformin associated with photodynamic therapy – A novel oncological direction. J Photochem Photobiol B. 2014 May 21;138C:80-91. [Epub ahead of print]

Sato T, Yasuzawa T, Uesaka A, Izumi Y, Kamiya A, Tsuchiya K, Kobayashi Y, Kuwahata M, Kido Y. Type 2 diabetic conditions in Otsuka Long-Evans Tokushima Fatty rats are ameliorated by 5-aminolevulinic acid. Nutr Res. 2014 Jun;34(6):544-51.

Leone A, Di Gennaro E, Bruzzese F, Avallone A, Budillon A.  New perspective for an old antidiabetic drug: metformin as anticancer agent. Cancer Treat Res. 2014;159:355-76.

Yin M, Zhou J, Gorak EJ, Quddus F.  Metformin is associated with survival benefit in cancer patients with concurrent type 2 diabetes: a systematic review and meta-analysis. Oncologist. 2013;18(12):1248-55.

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