Elucidating the synergistic mechanisms of MS17 and chrysin combination in human chemoresistant glioblastoma cells

Glioblastoma (GBM) constitutes the majority of all malignant adult brain tumors with five-year survival rates lower than 10% and a median survival of 12 to 18 months). The recommended standard of care to treat newly diagnosed GBM includes surgical resection followed by radiotherapy and concurrent oral intake of chemotherapy agent Temozolomide (TMZ). Although TMZ promotes tumour DNA damage, cell cycle arrest and apoptosis, GBM tumours are capable of developing various intrinsic and adaptive resistance mechanisms, leading the treatment to be ineffective. Despite this, TMZ remains the preferred option for GBM, with various severe side effects among patients. A popular approach to this ongoing resistance problem is the administration of drug combination therapies which could be more effective in treating GBM. In this project, we are looking into the potentiality of a natural product derivative to synergize effect and the anticancer mechanisms on TMZ in different GBM cell lines with different chemosensitivity. To date, no studies have reported on the anti-cancer activities and the mode of action of MS17 in human glioblastoma cells. We plan to use chrysin, a flavonoid that can be found in honey, propolis and passion flowers, with various anticancer activities in different cancer models. Our current data demonstrate chrysin as a potential synergistic agent that improves the efficacy of Temozolomide and lentinan. The addition of chrysin reduces their high IC50 value to suboptimal concentration, which further synergizes their anticancer activities in chemoresistance GBM cell lines. It is hypothesized combination of MS17 and chrysin will be able to demonstrate a greater anti-cancer activity through a synergism mode of action in chemoresistant GBM. Targeting these tumorigenic mechanisms may lead to future development of combined novel anti-glioblastoma drug therapy.