HY253, a novel compound isolated from Aralia continentalis, induces apoptosis via cytochrome c-mediated intrinsic pathway in HeLa cells

• Published in: Bioorganic & medicinal chemistry letters Vol. 19; no. 3; pp. 797 - 799
• Main Authors: Oh, Ha Lim, Lim, Haeyoung, Park, Younghee, Lim, Yoongho, Koh, Hyun Chul, Cho, Youl-Hee, Lee, Chul-Hoon
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01.02.2009; Elsevier
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Apoptosis; Apoptotic induction; Aralia; Aralia - metabolism; Aralia continentalis; Biological and medical sciences; Cytochrome c; Cytochromes c - metabolism; Drug Design; Drug Screening Assays, Antitumor; Enzyme Activation; Fluorenes - chemical synthesis; Fluorenes - pharmacology; General pharmacology; HeLa Cells; Humans; In Situ Nick-End Labeling; Magnetic Resonance Spectroscopy; Medical sciences; Mitochondria - metabolism; Models, Chemical; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Plant Extracts - chemical synthesis; Plant Extracts - pharmacology; Proto-Oncogene Proteins c-bcl-2 - metabolism; Cytochrome c; HeLa cells; Apoptotic induction; Aralia continentalis; Antineoplastic agent; Alcohol; Cytotoxicity; Uterine cervix; Medicinal plant; Dicotyledones; Angiospermae; Mechanism of action; Araliaceae; Tumor cell; Below ground plant part; Human; Root; Pharmacognosy; Tricyclic compound; In vitro; Hela cell line; Biological activity; Cell line; Plant origin; Isolation; Spermatophyta; Glycol; Structural analysis; Apoptosis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2008.12.009

The chemical structure of HY253, 7,8a-divinyl-2,4a,4b,5,6,7,8,8a,9,9a-decahydro-1H-fluorene-2,4a,4b,9a-tetraol. 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).