Combination of arsenic trioxide and ascorbic acid inhibits proliferation and induces apoptosis in human hepatoma cell line

    YAN Xiaoª²Yu, SHI Jianª²Guo, YAN Qingª²Guo, CHEN Shengª²Quan, ZHANG Zhiª²Pei, LI Qinª²Long, ZHANG Jing

    Department of Pathology, School of Basic Medicine, Fourth Military Medical University, Xi¬ðan 710033, China

    ¡¾Abstract¡¿ AIM: To study the synergistic effect of ascorbic acid (AA) and arsenic trioxide (As2O3) on the inhibition of proliferation and the induction of apoptosis in hepatoma cell line and to explore the effect of cellular glutathione (GSH) level on As2O3. METHODS: HepG2 cells were treated with As2O3 alone or in combination with AA. The viability of cells was determined by Trypanª²blue assay and subª²G1 cells were detected by flow cytometry (FCM). The apoptosis rate was assessed by AnnexinVª²PI staining and the GSH content was detected by GSH assay. RESULTS: 100 ¦Ìmol/L AA had no influence on the proliferation and apoptosis in HepG2 cells. With As2O3 at the dosage of 2 ¦Ìmol/L and 5 ¦Ìmol/L, the combination of As2O3 and AA effectively enhanced the growth inhibition, compared to separate use of either alone. The cells treated by the two agents potentiated the apoptosis rate, compared with that of As2O3 alone. When cells were treated with AA or As2O3, the intracellular GSH content decreased markedly. The intracellular GSH content decreased significantly in cells treated with two agents, compared with that of As2O3 alone. CONCLUSION: The intracellular GSH content plays an important role in As2O3. Combined use of AA and As2O3 can made HepG2 cells more sensitive to As2O3 by decreasing the GSH level. ......