Zerumbone induced apoptosis in liver cancer cells via modulation of Bax/Bcl-2 ratio.
BACKGROUND
Zerumbone is a cytotoxic component isolated from Zingiber zerumbet Smith, a herbal plant which is also known as lempoyang. This new anticancer bioactive compound from Z. zerumbet was investigated for its activity and mechanism in human liver cancer cell lines.


RESULTS
Zerumbone significantly showed an antiproliferative activity upon HepG2 cells with an IC50 of 3.45 +/- 0.026 microg/ml. Zerumbone was also found to inhibit the proliferation of non-malignant Chang Liver and MDBK cell lines. However the IC50 obtained was higher compared to the IC50 for HepG2 cells (> 10 microg/ml). The extent of DNA fragmentation was evaluated by the Tdt-mediated dUTP nick end labelling assay which showed that, zerumbone significantly increased apoptosis in HepG2 cells in a time-course manner. In detail, the apoptotic process triggered by zerumbone involved the up-regulation of pro-apoptotic Bax protein and the suppression of anti-apoptotic Bcl-2 protein expression. The changes that occurred in the levels of this antagonistic proteins Bax/Bcl-2, was independent of p53 since zerumbone did not affect the levels of p53 although this protein exists in a functional form. Western blotting analysis for Bax protein was further confirmed qualitatively with an immunoassay that showed the distribution of Bax protein in zerumbone-treated cells.


CONCLUSIONS
Therefore, zerumbone was found to induce the apoptotic process in HepG2 cells through the up and down regulation of Bax/Bcl-2 protein independently of functional p53 activity.
Sakinah
S A Sharifah
SA
School of Bioscience and Biotechnology, Faculty of Science and Technology, National University of Malaysia (UKM), 43600 Bangi, Selangor, Malaysia. shsakinah@yahoo.com
Handayani
S Tri
ST
Hawariah
L P Azimahtol
LP