HY253, a novel compound isolated from Aralia continentalis, induces apoptosis via cytochrome c-mediated intrinsic pathway in HeLa cells.
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 microM 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).
Oh
Ha Lim
HL
Department of Medical Genetics, College of Medicine, Hanyang University, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791, Republic of Korea.
Lim
Haeyoung
H
Park
Younghee
Y
Lim
Yoongho
Y
Koh
Hyun Chul
HC
Cho
Youl-Hee
YH
Lee
Chul-Hoon
CH
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D017209:Apoptosis; D027983:Aralia / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation; D005449:Fluorenes / Q000138:chemical synthesis* / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D009682:Magnetic Resonance Spectroscopy; D008928:Mitochondria / Q000378:metabolism; D008956:Models, Chemical; D010936:Plant Extracts / Q000138:chemical synthesis* / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
C539892:7,8a-divinyl-2,4a,4b,5,6,7,8,8a,9,9a-decahydro-1H-fluorene-2,4a,4b,9a-tetraol; D000970:Antineoplastic Agents; D005449:Fluorenes; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D045304:Cytochromes c