Metformin and Temozolomide synergistically enhanced effect against astrocytomas and GBM brain cancer

2015 Research

Treatment of Glioblastoma (GBM) brain cancer is still left wanting with the cancer resistant to many drugs, especially as many fail to get across the blood-brain barrier.

Prognosis is dismal and recurrence is often fast. The source of the relapse and even chemo-resistance has been identified several times as cancer stem cells at the heart of the tumour (1).

Temozolomide, or Temodar, is the UK’s drug of choice when dealing with GBM and astrocytomas. Unfortunately it is only of benefit to about 20 per cent of GBM patients. The rest have an over-expression of Methylguanine Methyltransferase (MGMT) and this causes resistance.

Metformin is a drug for type-2 diabetes. Primarily, it reduces blood sugar. 

But researchers have found added benefits:  In one study (2), Julie Sesen and a team of researchers showed metformin inhibited GBM cell growth, and affected metabolism in the mitochondria causing cell death (apoptosis).

Now researchers in China have confirmed that combining Temozolomide (TMZ) with Metformin (MET) synergistically inhibited proliferation and induced apoptosis – in both glioma cells and glioma stem cells (GSCs).

Combination of TMZ and MET significantly reduced the secondary gliosphere formation and expansion of GSCs.

TMZ in combination with MET synergistically inhibits the GSCs proliferation through down-regulation of AKT-mTOR signaling pathway.

Researchers from Jilin Hospital, China were clear that he combined treatment of two drugs inhibits GSCs self-renewal capability and partly eliminates the stem cells both in vitro and in vivo. Not only did metformin make Temozolomide work better, it widened the potential numbers of patients who would benefit

McGill University in America are conduction clinical trial using Temozolomide and metformin currently (3).

We have also covered research in the past that tricyclic anti-depressant drug chlomipramine was capable of causing apoptosis in GBM cells (4).

Boswellic acid also seems to improve the action of temozolomide.

Go to: Herb Berberine shown to have anti-tumour activity in GBM


References


1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4495393/

2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4395104/

3. https://clinicaltrials.gov/ct2/show/NCT02780024

4. https://www.onko-i.si/fileonko/datoteke/dokumenti/Radiology_40_2_3.pdf

5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3431946/


2015 Research
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