Verapamil potentiates anti-glioblastoma efficacy of temozolomide by modulating apoptotic signaling

Glioblastoma Multiforme (GBM) is the most malignant and invasive tumor of the CNS. Although temozolomide (TMZ) has improved the survival, long-lasting responses have not been reported. Therefore, there is a need to develop improved treatments, one of which might be newly identified drugs which can be used in combination therapy with low doses of standard drugs. Verapamil (VP) a known antihypertensive drug has been shown to enhance the activity of bis-chloroethylnitrosourea (BCNU), a drug used to treat GBM. Since, TMZ has replaced BCNU as the standard GBM chemotherapy; therefore, we aimed to study in vitro interaction of VP and TMZ against GBM. Anti-proliferative and apoptotic activities were studied using MTT, TUNEL assay and DAPI staining. Synergy was assessed using combination index method. Apoptotic markers were evaluated by RT-PCR, and immunocytochemistry. Both VP and TMZ significantly inhibited the growth of U87 cells in dose dependent manner. The combine effect of TMZ with VP was synergistic with a CDI value of