Apoptotic action of ursolic acid isolated from Corni fructus in RC-58T/h/SA#4 primary human prostate cancer cells

• Published in: Bioorganic & medicinal chemistry letters 2010-11, Vol.20 (22), p.6435-6438
• Main Authors: Kwon, Seong-Hyuk, Park, Hye-Young, Kim, Jae-Yong, Jeong, Il-Yun, Lee, Mi-Kyung, Seo, Kwon-Il
• Format: Article
• Language: English
• Subjects: Apoptosis; Apoptosis - drug effects; Biological and medical sciences; Cell Line, Tumor; Corni fructus; Cornus - chemistry; DNA Fragmentation; General pharmacology; Humans; Male; Medical sciences; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Primary human prostate cancer cells; Prostatic Neoplasms - enzymology; Prostatic Neoplasms - pathology; Triterpenes - isolation & purification; Triterpenes - pharmacology; Ursolic Acid
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2010.09.073

Ursolic acid from Corni fructus activated apoptosis in RC-58T/h/SA#4 cells via both caspase-dependent and -independent pathways. Ursolic acid (3β-hydroxy-urs-12-en-28-oic acid) is a major biological active component of Corni fructus that is known to induce apoptosis. However, the apoptotic mechanism of ursolic acid using primary malignant tumor (RC-58T/h/SA#4)-derived human prostate cells is not known. In the present study, ursolic acid significantly inhibited the growth of RC-58T/h/SA#4 cells in dose- and time-dependent manners. Ursolic acid induced cell death as evidenced by an increased proportion of cells in sub-G1 phase, the formation of apoptotic bodies, nuclear condensation, and DNA fragmentation. After ursolic acid treatment at concentrations above 40μM, the activities of caspase-3, -8, and -9 were significantly increased compared that of control. Ursolic acid modulated the upregulation of Bax (pro-apoptotic) as well as the downregulation of Bcl-2 (anti-apoptotic). Ursolic acid also stimulated Bid cleavage, which indicates that the apoptotic action of caspase-8-mediated Bid cleavage leads to the activation of caspase-9. Thus, the apoptotic effect of ursolic acid was involved in extrinsic and intrinsic signaling pathways. In addition, ursolic acid increased the expression of the caspase-independent mitochondrial apoptosis factor (AIF) in RC-58T/h/SA#4 cells. The present results suggest that ursolic acid from Corni fructus activated apoptosis in RC-58T/h/SA#4 cells via both caspase-dependent and -independent pathways.