METFORMIN AND ASPIRIN: NEW HOPE

Metformin:

It is a popular diabetes medication but two new clinical studies were  presented at the annual meeting of the American Association for Cancer Research. It was found that metformin may slow the rate of prostate cancer growth in certain patients, and in prolonging life for early-stage pancreatic cancer patients. The drug might have an effect against liver or oral tumors, as well as certain forms of melanoma and this study was done either in the lab or in animals. Metformin is also found to be effective against colon and breast cancer.

Anti-cancer mechanism of metformin is still unclear. It remains to be seen who would benefit the most from metformin. The most appropriate patients may be those with diabetes, those who are at risk for the disease or those whose tumors are sensitive to metformin.

Metformin

Metformin (Photo credit: Wikipedia)

In addition to suppressing hepatic glucose production, metformin increases insulin sensitivity, enhances peripheral glucose uptake (by phosphorylating GLUT-4 enhancer factor), increases fatty acid oxidation and decreases absorption of glucose from the gastrointestinal tract. Increased peripheral utilization of glucose may be due to improved insulin binding to insulin receptors.

Effect of insulin on glucose uptake and metabo...

Effect of insulin on glucose uptake and metabolism. Insulin binds to its receptor (1), which in turn starts many protein activation cascades (2). These include: translocation of Glut-4 transporter to the plasma membrane and influx of glucose (3), glycogen synthesis (4), glycolysis (5) and fatty acid synthesis (6). It works at other sizes, but sometimes truncates the text on the far right. (Photo credit: Wikipedia)

We know that cancer cell is abnormal cell which shows uncontrolled growth. Hence it needs more energy by glucose utilization. May be cancer cells are more sensitive to insulin. When healthy cells become less sensitive to insulin, cancer cell is more benefited by those circulating insulin. Moreover cancer cells get more glucose for utilization when glucose is not properly utilized by healthy cells. Metformin increases peripheral glucose utilization and insulin sensitivity in healthy cells and thus creates an energy crisis of cancer cells due to less availability of circulating insulin and glucose.

Aspirin:

Aspirin at 75 mg is prophylactically administered for heart attacts. At higher doses it is a popular analgesic, antpyratic and NSAID. Recent research shows that it may play a role in cancer prevention. It slows down the spread of cancer and metastasis. It is found to be effective in colon cancer.

Aspirin

Structure of aspirin

How does it work? The answer is not yet been confirmed. At low dose aspirin inhibits platelets  which promote clotting and also help cancer cells spread. Anti-inflammatory effect of cancer may slow down the swelling of cancer leison. It also prevent lymphatic metastasis by inhibiting VEGF-D-driven metastasis by interfering with the prostaglandin pathway and blocking lymphatic vessel dilation.

Main sites of metastases for some common cance...

Main sites of metastases for some common cancer types. Primary cancers are denoted by “…cancer” and their main metastasis sites are denoted by “…metastases”.(Photo credit: Wikipedia)

There is also a evidence that aspirin may prevent skin cancer. Patients taking aspirin or other NSAIDs had a 15% decreased risk for developing squamous cell carcinoma and a 13% lower risk of malignant melanoma. NSAIDs  did cut the risk of basal cell carcinomas developing on certain parts of the body other than the head and neck but NSAIDs can’t lower the overall risk of basal cell carcinoma – the most common and least aggressive type of skin cancer.

Other drugs:

Beta Blockers:

There is an interesting association of beta blockers with several cancer like nonsmall-cell lung cancer (NSCLC), breast cancer and malignant melanoma. Beta-blocker use is associated with improved distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) in NSCLC patients. Beta adrenergic receptor mediates tumor cell migration which is directly stimulated by noradrenaline. Beta adrenergic pathway can induce proliferation, invasion and migration of tumor cells which can lead to development of tumor in distant parts of the body. This pathway leads to Src activation via a unique protein kinase A (PKA)-mediated mechanism, which is critical to the regulation of cellular activity and cancer metastasis. Src (pronounced “sarc,” short for sarcoma) is a proto-oncogene – a normal gene that can become an oncogene due to increased expression – involved in the regulation of cell growth and division. When the adrenergic receptors on cancer cells are activated, they set into motion a chain of events that leads to formation of new blood vessels that feed tumor growth – a process known as angiogenesis. New blood vessel formation allows tumors to grow and spread more rapidly. Beta blockers inhibit this pathway and in doing so it can prevent the distant spread of tumor cells.

If we want to treat any cancer patient with beta blockers, we may need to know that is there any significant increase in biosynthesis of noradrenaline or any increased affinity of adrenergic receptor for noradrenaline in that particular patient body. It is necessary because adrenaline or noradrenaline is also beneficial for the body. May be there is any imbalance in the biosynthesis of this two in cancer patients. Further study is needed to establish anticancer effect of beta blocker.

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9 thoughts on “METFORMIN AND ASPIRIN: NEW HOPE

  1. Mohammad Arafat Siddiqui

    We know that cancer cell is abnormal cell which shows uncontrolled growth. Hence it needs more energy by glucose utilization. May be cancer cells are more sensitive to insulin. When healthy cells become less sensitive to insulin, cancer cell is more benefited by those circulating insulin. Moreover cancer cells get more glucose for utilization when glucose is not properly utilized by healthy cells. Metformin increases peripheral glucose utilization and insulin sensitivity in healthy cells and thus creates an energy crisis of cancer cells due to less availability of circulating insulin and glucose……..this is my thinking!

  2. Mohammad Arafat Siddiqui

    What do you think, what could be the anti-cancer mechanism of metformin???

  3. Keep going…..Good initiative….

  4. Mohammad Arafat Siddiqui

    Thanks….

  5. […] Metformin and Aspirin: New Hope (pharmaceuticalresearch.wordpress.com) Share this:TwitterFacebookLike this:LikeBe the first to like this post. Tags: Clomid, infertility, Lactose intolerance, metformin, PCOS, TTC […]

  6. Truman Burreson

    Aspirin is still the best pain killer today. The only bad side effect of aspirin is that it can cause gastric disturbance and in severe cases, it can cause ulcer. “`’., Yours trully health and wellness site

  7. what is the use of combining these two ??

    • Mohammad Arafat Siddiqui

      Anti cancer effect of metformin and aspirin is proved…….but I couldn’t find any evidence of combined effect…….of course it would be a good research to observe the combined effect. Thanks…..

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