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Lanatoside C의 항암 및 방사선 감수성 증가 효과​

Abstract

Cardiac glycosides are clinically used for cardiac arrhythmias. In this study, we investigated the mechanism responsible for anti-cancer and radiosensitizing effects of lanatoside C in colorectal cancer cells. Lanatoside C-treated cells showed classic patterns of autophagy, which may have been caused by lanatoside C-induced mitochondrial aggregation or degeneration. This mitochondrial dysfunction was due to disruption of K+ homeostasis, possibly through inhibition of Na+/K+-ATPase activity. In addition, lanatoside C sensitized HCT116 cells (but not HT-29 cells) to radiation in vitro. γ-H2AX, a representative marker of DNA damage, were sustained longer after combination of irradiation with lanatoside C, suggesting lanatoside C impaired DNA damage repair processes. Recruitment of 53BP1 to damaged DNA, a critical initiation step for DNA damage repair signaling, was significantly suppressed in lanatoside C-treated HCT116 cells. This may have been due to defects in the RNF8- and RNF168-dependent degradation of KDM4A/JMJD2A that increases 53BP1 recruitment to DNA damage sites. Although lanatoside C alone reduced tumor growth in the mouse xenograft tumor model, combination of lanatoside C and radiation inhibited tumor growth more than single treatments. Thus, lanatoside C could be a potential molecule for anti-cancer drugs and radiosensitizing agents.

Author information

Kang MA1, Kim MS1,2, Kim W1, Um JH3, Shin YJ4, Song JY5, Jeong JH1.​

1Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.

2Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.

3Korea Mouse Metabolic Phenotyping Center, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Korea.

4Department of Radiation Oncology, Inje University Sanggye Paik Hospital, Seoul, Korea.

5Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.