Treatment with Alstonia scholaris enhances radiosensitivity in vitro and in vivo

dThe radiosensitizing effect of 5 mug/mL of alkaloid fraction of Alstonia scholaris (ASERS) was evaluated in various neoplastic cell lines, namely: HeLa, HePG(2), HL60, MCF-7, and KB exposed to 0, 0.5, 1, 2, 3, and 4 Gy of gamma-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 HePG(2) 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) gamma-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.