Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 18 November 2021 / Approved: 19 November 2021 / Online: 19 November 2021 (14:54:40 CET)

How to cite: Lee, N.; Kwon, J.; Kang, A.; Song, J.; Hwang, S.; Um, H.; Kim, J.; Park, J.K. Radiosensitizer Effect of β-Apopicropodophyllin Against Colorectal Cancer via Induction of Reactive Oxygen Species and Apoptosis. Preprints 2021, 2021110366 (doi: 10.20944/preprints202111.0366.v1). Lee, N.; Kwon, J.; Kang, A.; Song, J.; Hwang, S.; Um, H.; Kim, J.; Park, J.K. Radiosensitizer Effect of β-Apopicropodophyllin Against Colorectal Cancer via Induction of Reactive Oxygen Species and Apoptosis. Preprints 2021, 2021110366 (doi: 10.20944/preprints202111.0366.v1).

Abstract

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 an-ti-cancer drug and can sensitize colorectal cancer (CRC) cells to radiation treatment. APP had an anti-cancer effect against the CRC cell lines HCT116, and DLD-1, SW480 and COLO320DM with IC50 values of 7.88 nM, and 8.22 nM, 9.84 nM and 7.757 nM, respec-tively induction of DNA damage. Colonogenic and cell counting assays indicated that the combined treatment of APP and γ-ionizing radiation (IR) showed greater retardation of cell growth than either alone, suggesting that APP sensitizes 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 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.

Keywords

β-Apopicropodophyllin; Radiosensitizer; Topoisomerase inhibitor; ROS, Apoptosis; Colorectal cancer

Subject

MEDICINE & PHARMACOLOGY, Pharmacology & Toxicology

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