HY251, a novel decahydrocyclopenta[a]indene analog, from Aralia continentalis induces apoptosis via down-regulation of AR expression in human prostate cancer LNCaP cells

• Published in: Bioorganic & medicinal chemistry letters 2011-03, Vol.21 (5), p.1347-1349
• Main Authors: Oh, Ha Lim, Lee, Chul-Hoon
• Format: Article
• Language: English
• Subjects: Androgen receptor; androgen receptors; antagonists; Antineoplastic agents; apoptosis; Apoptosis - drug effects; Apoptotic induction; Aralia; Aralia - chemistry; Aralia continentalis; Biological and medical sciences; caspase-9; Cell Line, Tumor; chemical structure; chemotherapy; cytochrome c; Down-Regulation - drug effects; gene expression regulation; General aspects; General pharmacology; genes; Humans; Indenes - chemistry; Indenes - pharmacology; LNCaP cells; Male; Medical sciences; mitochondria; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Plant Extracts - pharmacology; prostate-specific antigen; prostatic neoplasms; Prostatic Neoplasms - drug therapy; Receptors, Androgen - metabolism; roots; screening; Vinyl Compounds - chemistry; Vinyl Compounds - pharmacology; Western blotting
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2011.01.045

Effect of HY251, a novel decahydrocyclopenta[a]indene tetraol, on down-regulation of AR and PSA gene. In the course of screening for a novel anticancer drug candidate, we previously isolated HY251 with the molecular structure of 3-propyl-2-vinyl-1,2,3,3a,3b,6,7,7a,8,8a-decahydrocyclopenta[a]indene-3,3a,7a,8a-tetraol from the roots of Aralia continentalis. The current study was designed to evaluate the detailed mechanisms of apoptotic induction of HY251 in androgen-sensitive prostate cancer LNCaP cells. TUNEL assay and Western blot analysis revealed an appreciable apoptotic induction in LNCaP cells treated with 95 μM of HY251 for 24 h. This apoptotic induction is also associated with cytochrome c release from mitochondria which, in turn, resulted in the activation of caspase-9 and -3, and the cleavage of poly(ADP-ribose) polymerase (PARP). Moreover, we found that HY251 significantly inhibited the expression levels of androgen receptor (AR) and prostate-specific antigen (PSA) in a time-dependent manner, as well as abrogated up-regulation of AR and PSA genes with and without androgen. Therefore, we suggest that HY251, a novel androgen antagonist, may be a potent cancer chemotherapeutic candidate for the treatment of both androgen-sensitive and hormone-refractory prostate cancer.