Treatment with Alstonia scholaris Enhances Radiosensitivity In vitro and In vivo

Abstract

The radiosensitizing effect of 5 μg/mL of alkaloid fraction of Alstonia scholaris (ASERS) was evaluated in various neoplastic cell lines, namely: HeLa, HePG₂, HL60, MCF-7, and KB exposed to 0, 0.5, 1, 2, 3, and 4 Gy of γ-radiation. The irradiation of various cells caused a dose-dependent elevation in the cytotoxicity, and a maximum cytotoxic effect was observed at 4 Gy (the highest dose) in all the cell lines studied. The ASERS pretreatment increased the effect of radiation as evidenced by enhanced cell killing when compared with the concurrent phosphate-buffered saline (PBS) treated irradiation group. The greatest elevation in cell killing was observed for HeLa and KB cells, followed by HL60, MCF7, and HePG₂ cells. The in vitro observations were confirmed by in vivo studies, where the Ehrlich ascites carcinoma (EAC) bearing mice were treated with 120 mg/kg body weight of ASERS before exposure to 0, 1, 2, 4, 6, and 8 Gy of hemibody (below the rib cage) γ-radiation. Irradiation of EAC mice caused a dose-dependent tumor regression, as evidenced by increased life span of the animals. The pretreatment of tumor-bearing animals with 120 mg/kg ASERS resulted in a further remission in the tumor when compared with the concurrent nondrug-treated irradiated controls; as a result there was a radiation dose-dependent increase in the life span of tumor-bearing animals receiving 120 mg/kg ASERS, except for 8 Gy, where it was less than the concurrent control. The above findings corroborate with a time-dependent decrease in the glutathione (GSH) contents, accompanied by an increase in lipid peroxidation. Our study demonstrates that ASERS treatment enhances the effect of radiation and results in disease-free survival of the mice.