Radiosensitizer Effect of β-Apopicropodophyllin against Colorectal Cancer via Induction of Reactive Oxygen Species and Apoptosis

International Journal of Molecular Sciences

Joon Kim¹  Jin-Hee Kwon²  Sang-Gu Hwang²  Na-Gyeong Lee²  A-Ram Kang²  Jong Kuk Park²  Hong-Duck Um²  Jie-Young Song² 

[1] Division of Life Sciences, Korea University, Seoul 02841, Korea;Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Korea;

关键词: β-apopicropodophyllin;    radiosensitizer;    topoisomerase inhibitor;    ROS;    apoptosis;    colorectal cancer;   

DOI  :  10.3390/ijms222413514

来源: DOAJ

【 摘 要 】

β-apopicropodophyllin (APP), a derivative of podophyllotoxin (PPT), has been identified as a potential anti-cancer drug. This study tested whether APP acts as an anti-cancer drug and can sensitize colorectal cancer (CRC) cells to radiation treatment. APP exerted an anti-cancer effect against the CRC cell lines HCT116, DLD-1, SW480, and COLO320DM, with IC50 values of 7.88 nM, 8.22 nM, 9.84 nM, and 7.757 nM, respectively, for the induction of DNA damage. Clonogenic and cell counting assays indicated that the combined treatment of APP and γ-ionizing radiation (IR) showed greater retardation of cell growth than either treatment alone, suggesting that APP sensitized CRC cells to IR. Annexin V–propidium iodide (PI) assays and immunoblot analysis showed that the combined treatment of APP and IR increased apoptosis in CRC cells compared with either APP or IR alone. Results obtained from the xenograft experiments also indicated that the combination of APP and IR enhanced apoptosis in the in vivo animal model. Apoptosis induction by the combined treatment of APP and IR resulted from reactive oxygen species (ROS). Inhibition of ROS by N-acetylcysteine (NAC) restored cell viability and decreased the induction of apoptosis by APP and IR in CRC cells. Taken together, these results indicate that a combined treatment of APP and IR might promote apoptosis by inducing ROS in CRC cells.

【 授权许可】

Unknown