Abstract

Introduction: Ovarian cancer is the most lethal gynaecological malignancy in women. The use of chemotherapy for ovarian cancer treatment is effective in many patients, but it has been associated with serious side effects. Therefore, attention is given to natural compounds, including flavonoids as alternative drugs in cancer treatment and prevention. Objective: This study aims to determine the cytotoxicity of seven flavonoids, namely apigenin, biochanin A, flavone, fisetin, galangin, myricetin and 6- hydroxyflavone against two epithelial ovarian cancer cell lines (CAOV-3 and SKOV- 3). Method: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was carried out to determine the cell viability after being treated with selected flavonoids and carboplatin at 24, 48 and 72 h. The experiment was then followed by an AO/PI double staining assay using a fluorescent microscope to elucidate the morphological changes of cell death. Result: A total of four flavonoids, namely flavone, galangin, 6-hyroxyflavone and biochanin A showed highly cytotoxic against CAOV-3 cells at 24 h with lower IC50 value, ranging from 33.9 to 37.91 µgml^-1 compared with carboplatin 41.63 µgml^-1. Galangin has the lowest IC50 value among all at 48 h (26.16 µgml^-1) and 72 h (23.9 µgml^-1). Meanwhile, apigenin, 6-hydroxyflavone, flavone, biochanin A and myricetin exhibited less IC50 value than carboplatin (69.13 µgml^-1) of 36.55, 38.67, 38.78, 39.61 and 57.48 µgml^-1, respectively, at 24 h of SKOV- 3 cells treatment. Apigenin and biochanin A were detected to be highly cytotoxic in SKOV-3 cells at 48 and 72 h, respectively. The morphological changes of treated cells with flavonoids exhibited the presence of cell membrane blebbing and chromatin condensation indicating induction of apoptosis. Meanwhile, secondary necrosis was also seen in all flavonoids treatment after 24 h. Conclusion: This study shows that apigenin, myricetin, flavone, 6-hydroxyflavone and biochanin A can be potential therapeutic drugs in ovarian cancer.

Keywords: Flavonoid, CAOV-3, SKOV-3, Ovarian cancer