Genistein exerts potent antitumour effects alongside anaesthetic, propofol, by suppressing cell proliferation and nuclear factor-κB-mediated signalling and through upregulating microRNA-218 expression in an intracranial rat brain tumour model.

OBJECTIVE: This study was implemented to evaluate the effect of genistein and propofol on intracranial tumour model.

METHODS: Male Fischer 344 rats were subjected to intracranial implantation of 9L gliosarcoma cells. Genistein (100 or 200 mg/kg b.wt) was administered orally regularly from 3rd day after implantation to 25th day. Propofol (20 mg/kg; i.p.) was administered once every 5 days till 25th day and was administered 2 h after genistein.

KEY FINDINGS: Human gliosarcoma cells (U251) exposed to genistein (12.5-200 μg) for 24 h exhibited reduced cell viability as assessed by MTT assay and Hoechst staining. In intracranial tumour model, genistein treatment either with or without administration of propofol significantly reduced tumour volume and extended survival time of tumour-bearing rats. Genistein, either alone or with propofol upregulated pro-apoptotic proteins (Bad and Bax) and miRNA-218 expression and also had induced activation of cleaved caspase-3. Activated NF-κB signalling and overproduction of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) were reduced.

CONCLUSIONS: Genistein and propofol effectively inhibited growth of gliosarcoma cells and induced apoptosis. Genistein administration with propofol was found to be more effective than propofol or genistein alone suggesting the positive effects of genistein on propofol-mediated antitumour effects and vice versa.