Harmine Augments the Cytotoxic and Anti-invasive Potential of Temozolomide Against Glioblastoma Multiforme Cells

Abstract

Background: Glioblastoma multiforme (GBM) is considered the deadliest human cancer. Temozolomide is now a part of postresection standard chemotherapy for this type of cancer. Unfortunately, resistance to temozolomide is a major obstacle to treatment success. Combination therapy with natural anticancer agents increases the activity of temozolomide against cancer cells. Objectives: This study aimed to assess the effects of temozolomide in combination with harmine against GBM cells. Methods: Cancer cells were treated with temozolomide and/or harmine. After 24, 48, 72, and 96 h, the viability of the cells was assessed by the MTT test. The combination index and dose reduction index were determined by CompuSyn software. Tumor invasion potential was investigated by evaluating cell migration, invasion, and adhesion. The real-time PCR technique was done to study the expression pattern of two genes involved in cancer cell invasion. Statistical analysis was performed using one-way analysis of variance and Tukey’s post-hoc test, and differences were considered non-significant at P > 0.05. Results: After treatment with temozolomide, cell viability showed a concentration- and time-dependent decrease, and the cells’ survival rate decreased. The combination of temozolomide and harmine had a synergistic effect. Also, temozolomide and/or harmine treatment decreased cancer cells’ migration, invasion, and adhesion potentials, as well as the expression of metalloproteinases 2 and 9 in T98G cells. Conclusions: The combination of temozolomide and harmine can be promising for the successful treatment of GBM.