Evaluation of bromelain and temozolomide synergistic combination in human glioblastoma cells

The development of effective therapy is required for glioblastoma multiforme (GBM) patients because of the resistance action to temozolomide (TMZ). Bromelain (BRO) is a plant-derived therapeutic used against inflammation. The objective of this study is to appraise the effect of the BRO + TMZ combination on U87MG and LN229 cells and investigate its mechanism. The BRO + TMZ treatment resulted in synergistic effects that restricted cell growth and inhibited the colony formation of GBM cells. The combined treatment led to the initiation of early apoptosis resulting in the overexpression of BAX/caspase-3 (CASP3) and decreased transcript level of BCL-2. The BRO + TMZ induced the arrest in G0/G1 phase and decreased the migration mediated by the dysregulation of MMP-2 and MMP-9. The BRO and TMZ combination treatment was observed to be more effective than the individual compound to inhibit cell growth in human GBM cell lines.