The in vitro and in vivo anti-cancer activities of a standardized quassinoids composition from Eurycoma longifolia on LNCaP human prostate cancer cells

• Published in: PloS one Vol. 10; no. 3; p. e0121752
• Main Authors: Tong, Kind Leng, Chan, Kit Lam, AbuBakar, Sazaly, Low, Bin Seng, Ma, Hai Qiu, Wong, Pooi Fong
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.03.2015; Public Library of Science (PLoS)
• Subjects: Adenosine diphosphate; Androgen receptors; Androgens; Animals; Anticancer properties; Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Bioactive compounds; Cancer; Cell death; Cell Division - drug effects; Cell Line, Tumor; Charcoal; Composition; Cyclin D1; Cyclin D3; Cyclin-dependent kinase 2; Cyclin-dependent kinase 4; Cyclin-dependent kinase inhibitor p21; Dihydrotestosterone; Dihydrotestosterone - pharmacology; Diterpenes; Down-regulation; Eurycoma - chemistry; G1 phase; Growth factors; GTP-binding protein; Human papillomavirus; Humans; In Vitro Techniques; Infertility; Inhibition; Male; Medicine; Mice; Mice, Nude; Nuclei (cytology); Pharmaceutical sciences; Phase transitions; Plants (botany); Poly(ADP-ribose); Poly(ADP-ribose) polymerase; Prostate; Prostate cancer; Prostate-specific antigen; Prostatic Neoplasms - pathology; Proteins; Quassinoids; Quassins - isolation & purification; Quassins - pharmacology; Ribose; Secretion; Sexual behavior; Simaroubaceae; Testosterone; Translocation; Xenograft Model Antitumor Assays; Xenografts; Xenotransplantation; Kuala Lumpur Malaysia; Malaysia; United States > US; Penang Malaysia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0121752

Quassinoids are a group of diterpenoids found in plants from the Simaroubaceae family. They are also the major bioactive compounds found in Eurycoma longifolia which is commonly used as traditional medicine in South East Asia to treat various ailments including sexual dysfunction and infertility. These uses are attributed to its ability to improve testosterone level in men. Chronic consumption of E. longifolia extracts has been reported to increase testosterone level in men and animal model but its effect on prostate growth remains unknown. Therefore, the present study investigates the effects of a standardized total quassinoids composition (SQ40) containing 40% of the total quassinoids found in E. longifolia on LNCaP human prostate cancer cell line. SQ40 inhibited LNCaP cell growth at IC50 value of 5.97 μg/mL while the IC50 on RWPE-1 human prostate normal cells was 59.26 μg/mL. SQ40 also inhibited 5α-dihydrotestosterone-stimulated growth in LNCaP cells dose-dependently. The inhibitory effect of SQ40 in anchorage-independent growth of LNCaP cells was also demonstrated using soft agar assay. SQ40 suppressed LNCaP cell growth via G0/G1 phase arrest which was accompanied by the down-regulation of CDK4, CDK2, Cyclin D1 and Cyclin D3 and up-regulation of p21Waf1/Cip1 protein levels. SQ40 at higher concentrations or longer treatment duration can cause G2M growth arrest leading to apoptotic cell death as demonstrated by the detection of poly(ADP-ribose) polymerase cleavage in LNCaP cells. Moreover, SQ40 also inhibited androgen receptor translocation to nucleus which is important for the transactivation of its target gene, prostate-specific antigen (PSA) and resulted in a significant reduction of PSA secretion after the treatment. In addition, intraperitoneal injection of 5 and 10 mg/kg of SQ40 also significantly suppressed the LNCaP tumor growth on mouse xenograft model. Results from the present study suggest that the standardized total quassinoids composition from E. longifolia promotes anti-prostate cancer activities in LNCaP human prostate cancer cells.