HY251, a novel cell cycle inhibitor isolated from Aralia continentalis, induces G1 phase arrest via p53-dependent pathway in HeLa cells

• Published in: Bioorganic & medicinal chemistry letters Vol. 19; no. 3; pp. 959 - 961
• Main Authors: HA LIM OH, LIM, Haeyoung, CHO, Youl-Hee, HYUN CHUL KOH, HOJUNG KIM, LIM, Yoongho, LEE, Chul-Hoon
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 01-02-2009
• Subjects: Antineoplastic Agents - pharmacology; Aralia; Aralia - metabolism; Ataxia Telangiectasia Mutated Proteins; Biological and medical sciences; Cell Cycle - drug effects; Cell Cycle Proteins - metabolism; Chemistry, Pharmaceutical - methods; DNA-Binding Proteins - metabolism; Drug Screening Assays, Antitumor - methods; G1 Phase - drug effects; General pharmacology; HeLa Cells; Humans; Indenes - chemistry; Indenes - pharmacology; Magnetic Resonance Spectroscopy; Medical sciences; Models, Chemical; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Phosphorylation; Plant Extracts - metabolism; Plant Extracts - pharmacology; Protein-Serine-Threonine Kinases - metabolism; Tumor Suppressor Protein p53 - metabolism; Tumor Suppressor Proteins - metabolism; Vinyl Compounds - chemistry; Vinyl Compounds - pharmacology; Antineoplastic agent; Cell cycle progression; HY251; Uterine cervix; Medicinal plant; p53; Dicotyledones; Tertiary alcohol; Angiospermae; HeLa cells; Antimitotic; Araliaceae; Tumor cell; Below ground plant part; Human; G1 phase arrest; Root; Pharmacognosy; Tricyclic compound; In vitro; Hela cell line; Biological activity; G1 Phase; Cell line; Plant origin; Isolation; Spermatophyta; Aralia continentalis; Structural analysis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2008.11.087

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.