Cucurbitacin B and Evodiamine imparts anti‐neoplastic effects against Glioblastoma Multiforme via PI3‐K/AKT signaling pathway

Glioblastoma Multiforme (GBM) is a highly malignant and aggressive brain tumor. Patients' survival is around 6 to 12 months even with chemotherapy and surgery. Temozolomide is a first line chemotherapeutic treatment prescribed along with surgery but due to the high resistance to the drug and a low patient survival rate, new drugs and drug combinations must continue to be investigated and developed. Evodiamine, a marketed supplement, and Cucurbitacin B, a compound obtained from natural plants, have been identified as promising candidates to treat various neoplasms but has not been well studied in GBM, and especially in combination. The present study investigated the anti-proliferating effects of Evodiamine (Evo) and Cucurbitacin-B (CuB) individually and in combination in U-87MG cell line (Human Primary Glioblastoma cell line) and elucidated probable mechanisms of action via PI3K/AKT pathway in GBM. Results demonstrated that both CuB and Evo individually decreased the U-87MG cell viability in a dose dependent manner. The effect was pronounced with drug combination. CuB and Evo imparted their effect via the PI3K/P-AKT signaling pathway. In addition, Cells treated with CuB and Evo showed a decrease in Bcl2, an anti-apoptotic factor, and an increase in Bax, a pro-apoptotic factor, expression; a hallmark of induction of apoptosis. The increased expression of Cleaved Caspase-3 and p-c Jun have also been observed. Overall, Cucurbitacin and evodiamine individually and especially in combination proved to be potential anti-neoplastic agents in U-87MG cells and may be considered as potential adjuvant therapies for GBM.