Abstract

Zerumbone (ZER), a sesquiterpene in the rhizomes of Zingiber zerumbet Smith, was shown to exhibit antiproliferative activities on various cancer cells. This study was carried out to determine the cytotoxic and genotoxic effects of ZER on WEHI 7.2 wild type murine thymoma cells through the employment of standard MTT assay, alkaline comet assay and flow cytometry Annexin V/PI. Results from the MTT assay demonstrated that ZER has a dose-dependent but not a time-dependent cytotoxic effect towards WEHI 7.2 wild type cells with IC₅₀ values at 24, 48 and 72 hours were 3.02±0.20 µg/ml (13.832 µM), 2.73±0.13 µg/ml (12.503 µM) and 2.65±0.13 µg/ml (12.137 µM) respectively. Using IC₁₀ and IC₂₅ values obtained from the MTT assay, alkaline comet assay was carried out to detect DNA damage in ZER treated cells at three different time points (1/2 h, 1 h and 2 h). From the results, it was found that ZER induced significant DNA damage at all three time points for both concentrations (p < 0.05). Comparison of DNA damage levels at both concentrations suggested a concentration-dependent genotoxicity, as significantly higher values of tail DNA percentage and tail moment were obtained for cells treated with IC₂₅ concentration (p < 0.05). Furthermore, to understand the mode of cell death induced by ZER, flow cytometry Annexin V/PI was performed and it was found that cytotoxicity was achieved primarily via apoptosis. Collectively, ZER is able to induce genotoxicity in treated cells which subsequently leads to cytotoxicity via apoptosis and these presented characteristics suggest the compound as a potential anticancer drug.

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