RNase MC2: a new Momordica charantia ribonuclease that induces apoptosis in breast cancer cells associated with activation of MAPKs and induction of caspase pathways

Abstract

Ribonucleases (RNases) are ubiquitously distributed nucleases that cleave RNA into smaller pieces. They are promising drugs for different cancers based on their concrete antitumor activities in vitro and in vivo. Here we report for the first time purification and characterization of a 14-kDa RNase, designated as RNase MC2, in the seeds of bitter gourd (Momordica charantia). RNase MC2 manifested potent RNA-cleavage activity toward baker's yeast tRNA, tumor cell rRNA, and an absolute specificity for uridine. RNase MC2 demonstrated both cytostatic and cytotoxic activities against MCF-7 breast cancer cells. Treatment of MCF-7 cells with RNase MC2 caused nuclear damage (karyorrhexis, chromatin condensation, and DNA fragmentation), ultimately resulting in early/late apoptosis. Further molecular studies unveiled that RNase MC2 induced differential activation of MAPKs (p38, JNK and ERK) and Akt. On the other hand, RNase MC2 exposure activated caspase-8, caspase-9, caspase-7, increased the production of Bak and cleaved PARP, which in turn contributed to the apoptotic response. In conclusion, RNase MC2 is a potential agent which can be exploited in the worldwide fight against breast cancer.

Cytotoxicity of fractions derived from Crude Water Soluble Extract (CWSE) of Momordica charantia (Linn) Leaves on Lung, cervical and Breast cancer cells

“…The medicinal plant Momordica charantia (MC) has been named as one of such potent medicinal plants especially in relation to its usefulness in the treatment and management of cancers (Kubola and Siriamornpun, 2008). Quite a number of literatures have affirmed the antiproliferative effects of the plant on cancer cell lines (Lee-Huang et al, 2000;Yasui et al, 2005;Ray, et al, 2010;Fang et al, 2012). In our Lab, a number of preliminary tests carried out on this plant suggest it may be a potent inducer of apoptosis; the death a cell caused by its own self (Odewusi et al, 2010;Ehigie et al, 2013).…”

Leczyme: A New Candidate Drug for Cancer Therapy

“…RNases have various biological roles such as nutritional function, remobilization of phosphate, senescence, self-incompatibility, defensin-like activity, and RNA metabolism [16, 17]. Some RNases display angiogenic, neurotoxic, antitumor, or immunosuppressive activities [18].…”

X-Ray Crystallographic Structure of RNase Po1 That Exhibits Anti-tumor Activity

“…Almost all RNase A family members are non-toxic, but some RNases have been reported to exhibit anti-tumor activity. [31][32][33][34][35] RNases from Rana pipiens are the most extensively studied, and ranpirnase (Onconase) is currently in clinical trials as an anti-tumor drug. 36,37) The X-ray crystallographic structures of RNase A and Onconase have been reported.…”