Alantolactone and ZnO nanoparticles induce apoptosis activity of cisplatin in an ovarian cancer cell line (SKOV3)

Ovarian cancer is one of the leading causes of cancer mortality in women. Despite the increase in cases of this can cer, the current ther apeutic strategy is not effe ctive. This study aimed to investigate the effect of cisplatin (Cis) with alantolactone (ALT) and ZnO nanoparticles (ZnONPs) in inducing apoptosis in SKOV3 ovarian cancer cells line.

 To evaluate the viability of SKOV3 cells and determine the IC 50 of Cis, ALT, and ZnONPs, MTT assay was used. Real-time PCR and western blotting were used to evaluate the expression levels of genes (XIAP, cyclin D1, Bcl-2, Bax, and MDM2) and proteins (XIAP, cyclin D1, Bcl-2, Bax), respectively. Also, cellular ROS levels were assessed by fluorimetry.

Our results showed that ALT and ZnONPs significantly increased the response to Cis in SKOV3 cells compared to the control and this response is remarkably increased in the triple combination (ALT-Cis-ZnONPs). The expression of XIAP, cyclin D1, and Bcl-2 genes and proteins in the groups treated with ALT, Cis, and ZnONPs as a single agent, double and triple comb ination were significantly reduced compared to the control, while Bax was generally shown an increase. Also, the level of intracellular ROS is higher in the treatment groups than in the control group and the highest increase was observed in the triple combination.

Taken together, our data demonstrated the potential therapeutic approach of using ALT and ZnONPs that may enhance the apoptotic effects of Cis on the SKOV3 cells.