HY251, a novel cell cycle inhibitor isolated from Aralia continentalis, induces G1 phase arrest via p53-dependent pathway in HeLa cells.
This study was aimed to elucidate the novel structure of HY251 isolated from the roots of Aralia continentalis and to evaluate its detailed inhibition mechanisms on cell cycle progression in HeLa cells. The structure of HY251 was elucidated based on the interpretation of the NMR spectra, as 3-propyl-2-vinyl-1,2,3,3a,3b,6,7,7a,8,8a-decahydrocyclopenta[a]indene-3,3a,7a,8a-tetraol. The flow cytometric analysis revealed an appreciable G(1) phase arrest in HeLa cells treated with 100 microM of HY251. This HY251-induced G(1) phase arrest is associated with decreased expression of cyclin D3 and up-regulation of p21(CIP1) and p27(KIP1), via p53 phosphorylation at Ser-15 by transcriptional up-regulation of ATM, which resulted in increased hypophosphorylated pRb in HeLa cells.
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
Cho
Youl-Hee
YH
Koh
Hyun Chul
HC
Kim
Hojung
H
Lim
Yoongho
Y
Lee
Chul-Hoon
CH
D000970:Antineoplastic Agents / Q000494:pharmacology; D027983:Aralia / Q000378:metabolism*; D064007:Ataxia Telangiectasia Mutated Proteins; D002453:Cell Cycle / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004268:DNA-Binding Proteins / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D016193:G1 Phase / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D007192:Indenes / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D010766:Phosphorylation; D010936:Plant Extracts / Q000378:metabolism / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D014753:Vinyl Compounds / Q000737:chemistry / Q000494:pharmacology*
C539996:3-propyl-2-vinyl-1,2,3,3a,3b,6,7,7a,8,8a-decahydrocyclopenta(a)indene-3,3a,7a,8a-tetraol; D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D007192:Indenes; D010936:Plant Extracts; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D014753:Vinyl Compounds; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases