RADIOSENSITIZATION EFFECT OF ALPHA-MANGOSTIN ON CERVICAL CANCER (HELA) CELLS

Abstract

Radiotherapy (RT) is a common treatment for cervical cancer, but its effectiveness is often limited by tumor hypoxia and low radiosensitivity. Radiosensitizers that improve RT without increasing the dose are therefore of clinical interest. Alpha-Mangostin (AM), a xanthone from Garcinia mangostana, has anticancer and ROS-increasing properties. This study evaluated whether AM enhances radiosensitivity in vitro. Cytotoxicity (0–35 µM) was measured by the MTT assay, and radiation sensitivity (0–6 Gy) was assessed through clonogenic survival. ROS detection assay, γ-H2AX immunofluorescence, cell cycle analysis, apoptosis measurement, and clonogenic survival tests were used to examine the radiosensitization effect. AM showed dose-dependent cytotoxicity in HeLa cells, with an inhibitory concentration 20 (IC20) of 13.67 µM, while sparing fibroblasts. The radiation lethal dose 20 (LD20) was 1.4 Gy. However, the combination treatment used AM at 12 µM (IC14) with 2 Gy (LD30) irradiation (IR) to avoid 50% cell death. AM increased G2/M arrest by 21.10% (p < 0.01) compared to controls. The combined treatment caused a 4.07-fold increase in oxidative stress relative to the control (p < 0.0001), which was higher than either AM alone or IR alone. Additionally, this combination increased γ-H2AXpositive cells to 48.2% (p < 0.0001), raised apoptosis to 39.48% (p < 0.0001), and reduced clonogenic survival to 28% (p < 0.0001) compared to RT alone. This resulted in a sensitizer enhancement ratio (SER) of 2.48. Therefore, AM effectively radiosensitized HeLa cells by increasing oxidative stress, promoting DNA double-strand breaks, and inducing G2/M arrest.