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Apoptosis

, Volume 17, Issue 4, pp 377–387 | Cite as

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

  • Evandro Fei Fang
  • Chris Zhi Yi Zhang
  • Wing Ping Fong
  • Tzi Bun Ng
Original Paper

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.

Keywords

Momordica charantia Ribonuclease Breast cancer Therapy Caspase pathway 

Abbreviations

RNase MC2

The second ribonuclease reported from Momordica charantia

MAPKs

Mitogen-activated protein kinases

BG

Bitter gourd (Momordica charantia)

Notes

Conflicts of interest

The authors declare that they have no conflicts of interest.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Evandro Fei Fang
    • 1
  • Chris Zhi Yi Zhang
    • 2
    • 3
  • Wing Ping Fong
    • 4
  • Tzi Bun Ng
    • 1
    • 5
  1. 1.School of Biomedical Sciences, Faculty of MedicineThe Chinese University of Hong KongShatinHong Kong
  2. 2.State Key Laboratory of Oncology in Southern ChinaSun Yat-Sen University Cancer CenterGuangzhouChina
  3. 3.Department of PathologySun Yat-Sen University Cancer CenterGuangzhouChina
  4. 4.School of Life Sciences, Faculty of ScienceThe Chinese University of Hong KongShatinHong Kong
  5. 5.Choh Ming Li Basic Medical Sciences BuildingThe Chinese University of Hong KongShatinHong Kong

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