Investigating the effect of hydroalcoholic extract of Prosopis farcta fruit on the toxicity induced by temozolomide in glioblastoma cell line in vitro

Abstract

Introduction: Glioblastoma multiforme (GBM) is one of the most common human brain tumors. The use of temozolomide drug can be mentioned among the treatment methods. Researchers are trying to use methods to overcome resistance to temozolomide. Regarding the anticancer effects of Prosopis farcta in traditional Iranian medicine, the present study aimed to investigate the effect of the fruit hydroalcoholic extract of Prosopis farcta on the toxicity induced by temozolomide in the GBM cell line. Method: The T98G cell line was treated with plant extract and temozolomide. The cell survival rate was evaluated by MTT assay. The type of interaction between herbal extract and temozolomide was evaluated using the MTT test and Compusyn software. In addition, the amount of nitric oxide production in cancer cells was measured. Furthermore, the expression of the O-6-Methylguanine-DNA Methyltransferase (MGMT) gene was evaluated by Real-time PCR. Results: Hydroalcoholic extract of the plant and temozolomide decreased cell viability in a concentration- and time-dependent manner. The combination of extract and temozolomide had a synergistic effect in reducing cell survival. The hydroalcoholic extract and/or temozolomide caused a significant decrease in nitric oxide production and secretion (P<0.05). Considering the expression of MGMT, the hydroalcoholic extract and temozolomide significantly decreased and increased the expression of this gene, respectively (P<0.05). Simultaneous treatment caused a significant decrease in MGMT expression compared to the group treated with temozolomide (P<0.05). Conclusion: The combination of Prosopis farcta fruit extract and temozolomide had synergistic antitumor potential in GBM cells. This extract could reduce cellular resistance to temozolomide through the downregulation of MGMT expression.