title: In vitro and in vivo anticarcinogenic effects of RNase MC2, a ribonuclease isolated from dietary bitter gourd, toward human liver cancer cells.
abstract: Hepatocellular carcinoma (HCC) constitutes a predominant part of primary liver cancer which ranks as the fifth most common cancer as well as the third most common cause of cancer mortality. In view of the poor prognosis of unresectable liver cancers, it is of pivotal importance to develop novel chemotherapeutical regimens. RNase MC2 is a 14-kDa ribonuclease isolated from dietary bitter gourd (Momordica charantia) that manifested antitumor potential against breast cancers. In this study, we investigated the potential application of RNase MC2 on Hep G2 cells. We showed that RNase MC2 inhibited cell proliferation and induced cell apoptosis in both in vitro and in vivo studies. RNase MC2 treatment caused cell cycle arrest predominantly at the S-phase and apoptosis, which is associated with the activation of both caspase-8 and caspase-9 regulated caspase pathways. Our further investigation disclosed that RNase MC2 down-regulated the anti-apoptotic protein Bcl-2 and increased the expression of pro-apoptotic protein Bak. Moreover, the phosphorylation of ERK and JNK was involved in the apoptosis process. Importantly, RNase MC2 significantly suppressed the growth of Hep G2 xenograft-bearing nude mice by inducing apoptosis. This notion is supported by data indicating an increased number of caspase-3- and PARP-positive cells, and TUNEL-positive cells in RNase MC2-treated tumor tissues. In summary, we have revealed the antitumor potential of RNase MC2 toward Hep G2 cells. Considering that bitter gourd is a common dietary component in many countries, this study may help to prompt the clinical application of RNase MC2.
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong. fangfei1030@yahoo.com.cn
authors.forename: Evandro Fei
authors.initials: EF
authors.lastname: Fang
authors.forename: Chris Zhi Yi
authors.initials: CZ
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Wing Ping
authors.initials: WP
authors.lastname: Fong
authors.forename: Tzi Bun
authors.initials: TB
authors.lastname: Ng
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D020169:Caspases / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D029777:Momordica charantia / Q000201:enzymology*; D010940:Plant Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012260:Ribonucleases / Q000302:isolation & purification / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D010940:Plant Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D011065:Poly(ADP-ribose) Polymerases; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; C575809:RNase MC2, Momordica charantia; D012260:Ribonucleases; D020169:Caspases