Fangchinoline induced G1/S arrest by modulating expression of p27, PCNA, and cyclin D in human prostate carcinoma cancer PC3 cells and tumor xenograft

• Published in: Bioscience, biotechnology, and biochemistry biotechnology, and biochemistry, 2010, Vol.74 (3), p.488-493
• Main Authors: Wang, C.D., Huazhong Univ. of Science and Technology, Wuhan (China), Huang, J.G, Gao, X, Li, Y, Zhou, S.Y, Yan, X, Zou, A, Chang, J.L, Wang, Y.S, Yang, G.X, He, G.Y
• Format: Article
• Language: English
• Subjects: ANIMAL GROWTH PROMOTERS; Animals; ANTIBIOTICOS; ANTIBIOTICS; ANTIBIOTIQUE; Antineoplastic Agents - pharmacokinetics; APOPTOSE; APOPTOSIS; Apoptosis - drug effects; bcl-2-Associated X Protein - metabolism; Benzylisoquinolines - pharmacology; Biological and medical sciences; CARCINOMA; Carcinoma - metabolism; CARCINOME; Caspase 3 - metabolism; Cell Line, Tumor; Cell Proliferation - drug effects; Cyclin D - antagonists & inhibitors; Cyclin D - metabolism; Cyclin-Dependent Kinase Inhibitor p27 - metabolism; DRUG THERAPY; EXPRESION GENICA; EXPRESSION DES GENES; fangchinoline; Fundamental and applied biological sciences. Psychology; G2 Phase - drug effects; GENE EXPRESSION; http://www.fao.org/aos/agrovoc#c_1314; http://www.fao.org/aos/agrovoc#c_2394; http://www.fao.org/aos/agrovoc#c_24407; http://www.fao.org/aos/agrovoc#c_27527; http://www.fao.org/aos/agrovoc#c_3398; http://www.fao.org/aos/agrovoc#c_35587; http://www.fao.org/aos/agrovoc#c_36634; http://www.fao.org/aos/agrovoc#c_492; human prostate cancer cell lines (PC3); Humans; Male; Mice; Mice, Nude; Proliferating Cell Nuclear Antigen - metabolism; PROMOTEUR DE CROISSANCE ANIMALE; PROMOTORES DEL CRECIMIENTO ANIMAL; PROSTATA; PROSTATE; prostate cancer; Prostatic Neoplasms - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; S Phase - drug effects; STEPHANIA; TERAPEUTICA MEDICAMENTOSA; THERAPEUTIQUE MEDICAMENTEUSE; tumor xenograft; Xenograft Model Antitumor Assays
• ISSN: 0916-8451; 1347-6947
• DOI: 10.1271/bbb.90490

Prostate cancer (PCA) is the most common invasive malignancy and the second leading cause of cancer-related death in males. The present study investigated the effects of fangchinoline (Fan), an important compound in Stephania Tetradra S. Moore (Fenfangji) with pain-relieving, blood pressure-depressing, and antibiotic activities, on human PCA. It was found that Fan inhibited human prostate cancer cell lines (PC3) cell proliferation in a dose- and time-dependent manner. Studies of cell-cycle progression showed that the anti-proliferative effect of Fan was associated with an increase in the G1/S phase of PC3 cells. Western blot results indicated that Fan-induced G1/S phase arrest was mediated through inhibition of cyclin-regulated signaling pathways. Fan induced p27 expression and inhibited cyclin D and proliferating cell nuclear antigen (PCNA) expression in PC3 cells. Increased exposure time to Fan caused apoptosis of PC3 cells, which was associated with up-regulation of pro-apoptotic proteins Bax and caspase 3, and down-regulation of anti-apoptotic protein Bcl-2. Furthermore, Fan had anti-tumorigenic activity in vivo, including reduction of tumor volume and pro-apoptotic and anti-proliferative effects in a PC3 nude mouse xenograft. Taking all this together, it can be concluded that Fan is an effective anti-proliferative agent that modulates cell growth regulators in prostate cancer cells.