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Garcinol Alone and in Combination With Cisplatin Affect Cellular Behavior and PI3K/AKT Protein Phosphorylation in
Jie Zhang1, Huan Fang2, Jinguo Zhang3
1Department of Clinical Nutrition, Jinshan Hospital, Fudan University, Shanghai, China.
Abstract:
Garcinol is a plant-derived compound that has some physiological benefits to human cells. However, the effect of garcinol on ovarian cancer (OC) cell proliferation and apoptosis is unknown. The current study aimed to examine the effects of garcinol alone and in combination with cisplatin (DDP) on cellular behavior and to explore the expression pattern of PI3K/AKT and nuclear factor-κB (NF-κB) in human OC cells. We found that OVCAR-3 cell viability was decreased after garcinol treatment. Garcinol alone and in combination with DDP significantly inhibited cell proliferation and had a synergistic effect evaluated by CompuSyn software. The cell cycle analysis showed the S phase arrest by garcinol. Furthermore, garcinol alone and in combination with DDP promoted cell apoptosis. The garcinol-induced apoptosis was further confirmed by the detection of cleavage forms of PARP and caspase 3. An increase in proapoptotic factor Bax expression was also found in garcinol-treated cells. Moreover, garcinol significantly decreased the phosphorylation of PI3K and AKT proteins and downregulated the expression of NF-κB. Thus, our data demonstrated that garcinol has the potential to be used as an anticancer agent and may synergize the effect of DDP. These actions are most likely through the regulation of the PI3K/AKT and NF-κB pathways.
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