1′-Acetoxychavicol acetate promotes caspase 3-activated glioblastoma cell death by overcoming enhanced cytokine expression

Abstract

The brain consumes ∼20% of the oxygen utilized in the human body, meaning that brain tumors are vulnerable to paradoxical physiological effects from free radical generation. In the present study, 1′-acetoxychavicol acetate (ACA), a naturally derived antioxidant that inhibits xanthine oxidase, was evaluated for its role as an anti-tumorigenic agent in glioblastomas. The study revealed that ACA inhibited glioblastoma cell proliferation as a consequence of promoting apoptotic cell death by enhancing caspase 3 activity. It was also shown that ACA impaired the migratory ability of glioblastoma cells by decreasing their adhesive properties. Additionally, ACA increased the protein expression levels of the pro-survival signaling cytokines, IL-6 and IL-1α, established cell protectors and survival molecules in brain tumors. Together, these results demonstrate that, despite enhanced expression of compensatory signaling molecules that contribute to tumor cell survival, ACA is an effective pro-apoptotic inducing agent in glioblastomas.