Bromelain inhibits nuclear factor kappa-B translocation, driving human epidermoid carcinoma A431 and melanoma A375 cells through G2/M arrest to apoptosis
Article first published online: 22 MAR 2011
Copyright ©2011 Wiley Periodicals, Inc.
Special Issue: Theme Issue: Phytochemicals for the Prevention and Treatment of Cancer
Volume 51, Issue 3, pages 231–243, March 2012
How to Cite
Bhui, K., Tyagi, S., Srivastava, A. K., Singh, M., Roy, P., Singh, R. and Shukla, Y. (2012), Bromelain inhibits nuclear factor kappa-B translocation, driving human epidermoid carcinoma A431 and melanoma A375 cells through G2/M arrest to apoptosis. Mol. Carcinog., 51: 231–243. doi: 10.1002/mc.20769
- Issue published online: 12 JAN 2012
- Article first published online: 22 MAR 2011
- Manuscript Accepted: 18 FEB 2011
- Manuscript Revised: 29 JAN 2011
- Manuscript Received: 20 AUG 2010
- nuclear factor-κB;
- G2/M arrest;
- anchorage-independent growth
Bromelain, obtained from pineapple, is already in use clinically as adjunct in chemotherapy. Our objective was to test its ability to act as a sole anti-cancer agent. Therefore, we describe its anti-proliferative, anti-inflammatory and subsequent anti-cancer effects in vitro, against human epidermoid carcinoma-A431 and melanoma-A375 cells. Bromelain exhibited reduction in proliferation of both these cell-lines and suppressed their potential for anchorage-independent growth. Further, suppression of inflammatory signaling by bromelain was evident by inhibition of Akt regulated-nuclear factor-kappaB activation via suppression of inhibitory-kappaBα phosphorylation and concomitant reduction in cyclooxygenase-2. Since, the inflammatory cascade is well-known to be closely allied to cancer; we studied the effect of bromelain on events/molecules central to it. Bromelain caused depletion of intracellular glutathione and generation of reactive oxygen-species followed by mitochondrial membrane depolarization. This led to bromelain-induced cell-cycle arrest at G2/M phase which was mediated by modulation of cyclin B1, phospho-cdc25C, Plk1, phospho-cdc2, and myt1. This was subsequently followed by induction of apoptosis, indicated by membrane-blebbing, modulation of Bax-Bcl-2 ratio, Apaf-1, caspase-9, and caspase-3; chromatin-condensation, increase in caspase-activity and DNA-fragmentation. Bromelain afforded substantial anti-cancer potential in these settings; hence we suggest it as a potential prospect for anti-cancer agent besides only an additive in chemotherapy. © 2011 Wiley Periodicals, Inc.