Asperlin induces G2/M arrest through ROS generation and ATM pathway in human cervical carcinoma cells |
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| Authors: | Long He Mei-Hua Nan Hyun Cheol Oh Young Ho Kim Jae Hyuk Jang Raymond Leo Erikson Jong Seog Ahn Bo Yeon Kim |
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| Institution: | aChemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk 363-883, Republic of Korea;bCollege of Medical and Life Sciences, Silla University, 100 Silladaehak-gil, Sasang-gu, Busan 617-736, Republic of Korea;cCollege of Pharmacy, ChungNam National University, Yuseong, Daejeon, 305-764, Republic of Korea;dDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA;eWorld Class Institute, KRIBB, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk 363-883, Republic of Korea |
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| Abstract: | We exploited the biological activity of an antibiotic agent asperlin isolated from Aspergillus nidulans against human cervical carcinoma cells. We found that asperlin dramatically increased reactive oxygen species (ROS) generation accompanied by a significant reduction in cell proliferation. Cleavage of caspase-3 and PARP and reduction of Bcl-2 could also be detected after asperlin treatment to the cells. An anti-oxidant N-acetyl-l-cysteine (NAC), however, blocked all the apoptotic effects of asperlin. The involvement of oxidative stress in asperlin induced apoptosis could be supported by the findings that ROS- and DNA damage-associated G2/M phase arrest and ATM phosphorylation were increased by asperlin. In addition, expression and phosphorylation of cell cycle proteins as well as G2/M phase arrest in response to asperlin were significantly blocked by NAC or an ATM inhibitor KU-55933 pretreatment. Collectively, our study proved for the first time that asperlin could be developed as a potential anti-cancer therapeutics through ROS generation in HeLa cells. |
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| Keywords: | Asperlin ROS ATM |
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