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HY253, a novel compound isolated from Aralia continentalis,induces apoptosis via cytochrome c-mediated intrinsic pathway in HeLa cells
Authors:Ha Lim Oh  Haeyoung Lim  Younghee Park  Yoongho Lim  Hyun Chul Koh  Youl-Hee Cho  Chul-Hoon Lee
Institution:1. Department of Medical Genetics, College of Medicine, Hanyang University, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791, Republic of Korea;2. Department of Pharmacology, College of Medicine, Hanyang University, Seoul 133-791, Republic of Korea;3. Bio/Molecular Informatics Center, Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea
Abstract:This study was aimed to elucidate the novel structure of HY253 isolated from the roots of Aralia continentalis and to evaluate its detailed mechanisms on apoptotic induction in HY253-treated HeLa cells. The structure of HY253 was elucidated based on the interpretation of the NMR spectra, as 7,8a-divinyl-2,4a,4b,5,6,7,8,8a,9,9a-decahydro-1H-fluorene-2,4a,4b,9a-tetraol. The TUNEL assay using flow cytometer revealed an appreciable apoptotic induction in HeLa cells treated with 100 μM of HY253 for 48 h. This apoptotic induction is associated with cytochrome c release from mitochondria, via up-regulation of pro-apoptotic Bcl-2 proteins, such as Bax and Bak, which, in turn, resulted in the activation of caspase-8, -9 and -3, and the cleavage of poly(ADP-ribose) polymerase (PARP).
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