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

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-depressi...

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Bibliographic Details
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
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Summary: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.
ISSN:0916-8451
1347-6947
DOI:10.1271/bbb.90490