| Summary: | <p>Abstract</p> <p>Background</p> <p>Zerumbone is a cytotoxic component isolated from <it>Zingiber zerumbet </it>Smith, a herbal plant which is also known as lempoyang. This new anticancer bioactive compound from <it>Z. zerumbet </it>was investigated for its activity and mechanism in human liver cancer cell lines.</p> <p>Results</p> <p>Zerumbone significantly showed an antiproliferative activity upon HepG2 cells with an IC50 of 3.45 ± 0.026 μg/ml. Zerumbone was also found to inhibit the proliferation of non-malignant Chang Liver and MDBK cell lines. However the IC<sub>50 </sub>obtained was higher compared to the IC<sub>50 </sub>for HepG2 cells (> 10 μg/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.</p> <p>Conclusion</p> <p>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.</p>
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