Ribosome-inactivating proteins isolated from dietary bitter melon induce apoptosis and inhibit histone deacetylase-1 selectively in premalignant and malignant prostate cancer cells.

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.

• Authors: Su Dao Xiong, Kang Yu, Xin Hua Liu, Li Hui Yin, Alexander Kirschenbaum, Shen Yao, Goutham Narla, Analisa DiFeo, Jian Buo Wu, Yong Yuan, Shuk-Mei Ho, Ying Wai Lam, Alice C Levine
• Journal: International journal of cancer (Int J Cancer) Vol. 125 Issue 4 Pg. 774-82 (Aug 15 2009) ISSN: 1097-0215 [Electronic] United States
• PMID: 19384952 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Histone Deacetylase Inhibitors
• Plant Proteins
• RNA, Messenger
• Luciferases
• Proto-Oncogene Proteins c-akt
• PTEN Phosphohydrolase
• Ribosome Inactivating Proteins
• HDAC1 protein, human
• Histone Deacetylase 1
• Histone Deacetylases

Topics

• 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, metabolism)
• Phosphorylation
• Plant Proteins (isolation & purification, pharmacology)
• Precancerous Conditions (enzymology, pathology)
• Prostatic Intraepithelial Neoplasia (genetics, metabolism, pathology)
• Prostatic Neoplasms (enzymology, pathology)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• RNA, Messenger (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Ribosome Inactivating Proteins (isolation & purification, pharmacology)
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization