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Induction of G1 arrest and apoptosis in androgen-dependent human prostate cancer by Kuguacin J, a triterpenoid from Momordica charantia leaf.
- Source :
-
Cancer letters [Cancer Lett] 2011 Jul 28; Vol. 306 (2), pp. 142-50. Date of Electronic Publication: 2011 Mar 22. - Publication Year :
- 2011
-
Abstract
- In this study, we focused on the effects of a bitter melon (Momordica charantia) leaf extract (BMLE) and a purified component, Kuguacin J (KuJ), on androgen-dependent LNCaP human prostate cancer cells. Both treatments exerted growth inhibition through G1 arrest and induction of apoptosis. In addition, KuJ markedly decreased the levels of cyclins (D1 and E), cyclin-dependent kinases (Cdk2 and Cdk4) and proliferating cell nuclear antigen, and caused an increase in p21 and p27 levels. Its induction of apoptosis was accompanied by an increase in cleavage of caspase-3 and poly (ADP-ribose) polymerase, attributable to augment of Bax/Bcl-2 and Bad/Bcl-xL and reduction of survivin levels. BMLE and KuJ also reduced the expression of androgen receptor (AR), prostate-specific antigen (PSA) while induced P53 protein level. Down-regulation of p53 by RNA interference indicated that BMLE and KuJ inhibited cell growth partly through p53-dependent cell cycle arrest and apoptotic pathways. Both BMLE and KuJ caused less toxicity in a normal prostate cell line, PNT1A. Our results suggest that BMLE and a purified component, KuJ, from its diethyl ether fraction could be promising candidate new antineoplastic and chemopreventive agents for androgen-dependent prostate cancer and carcinogenesis.<br /> (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)
- Subjects :
- Blotting, Western
Cell Cycle Proteins
Cell Proliferation drug effects
Humans
Male
Neoplasms, Hormone-Dependent drug therapy
Neoplasms, Hormone-Dependent metabolism
Prostatic Neoplasms metabolism
Tumor Cells, Cultured
Apoptosis drug effects
G1 Phase drug effects
Momordica charantia chemistry
Neoplasms, Hormone-Dependent pathology
Plant Leaves chemistry
Prostatic Neoplasms drug therapy
Prostatic Neoplasms pathology
Triterpenes pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7980
- Volume :
- 306
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cancer letters
- Publication Type :
- Academic Journal
- Accession number :
- 21429659
- Full Text :
- https://doi.org/10.1016/j.canlet.2011.02.041