Title: Ribosome-inactivating proteins isolated from dietary bitter melon induce apoptosis and inhibit histone deacetylase-1 selectively in premalignant and malignant prostate cancer cells.
Authors: Xiong, Su Dao; Yu, Kang; Liu, Xin Hua; Yin, Li Hui; Kirschenbaum, Alexander; Yao, Shen; Narla, Goutham; DiFeo, Analisa; Wu, Jian Buo; Yuan, Yong; Ho, Shuk-Mei; Lam, Ying Wai; Levine, Alice C
Published In Int J Cancer, (2009 Aug 15)
Abstract: Epidemiologic evidence suggests that a diet rich in fruits and vegetables is associated with a reduced risk of prostate cancer (PCa) development. Although several dietary compounds have been tested in preclinical PCa prevention models, no agents have been identified that either prevent the progression of premalignant lesions or treat advanced disease. Momordica charantia, known as bitter melon in English, is a plant that grows in tropical areas worldwide and is both eaten as a vegetable and used for medicinal purposes. We have isolated a protein, designated as MCP30, from bitter melon seeds. The purified fraction was verified by SDS-PAGE and mass spectrometry to contain only 2 highly related single chain Type I ribosome-inactivating proteins (RIPs), alpha-momorcharin and beta-momorcharin. MCP30 induces apoptosis in PIN and PCa cell lines in vitro and suppresses PC-3 growth in vivo with no effect on normal prostate cells. Mechanistically, MCP30 inhibits histone deacetylase-1 (HDAC-1) activity and promotes histone-3 and -4 protein acetylation. Treatment with MCP30 induces PTEN expression in a prostatic intraepithelial neoplasia (PIN) and PCa cell lines resulting in inhibition of Akt phosphorylation. In addition, MCP30 inhibits Wnt signaling activity through reduction of nuclear accumulation of beta-catenin and decreased levels of c-Myc and Cyclin-D1. Our data indicate that MCP30 selectively induces PIN and PCa apoptosis and inhibits HDAC-1 activity. These results suggest that Type I RIPs derived from plants are HDAC inhibitors that can be utilized in the prevention and treatment of prostate cancer.
PubMed ID: 19384952
MeSH Terms: Animals; Apoptosis/drug effects*; Blotting, Western; Cell Cycle; Diet; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Histone Deacetylase 1; Histone Deacetylase Inhibitors*; Histone Deacetylases/metabolism; Humans; Immunoblotting; In Situ Nick-End Labeling; Luciferases/metabolism; Male; Mice; Mice, Nude; Momordica charantia/chemistry*; PTEN Phosphohydrolase/genetics; PTEN Phosphohydrolase/metabolism; Phosphorylation; Plant Proteins/isolation & purification; Plant Proteins/pharmacology*; Precancerous Conditions/enzymology; Precancerous Conditions/pathology*; Prostatic Intraepithelial Neoplasia/genetics; Prostatic Intraepithelial Neoplasia/metabolism; Prostatic Intraepithelial Neoplasia/pathology; Prostatic Neoplasms/enzymology; Prostatic Neoplasms/pathology*; Proto-Oncogene Proteins c-akt/genetics; Proto-Oncogene Proteins c-akt/metabolism; RNA, Messenger/genetics; RNA, Messenger/metabolism; Reverse Transcriptase Polymerase Chain Reaction; Ribosome Inactivating Proteins/isolation & purification; Ribosome Inactivating Proteins/pharmacology*; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization