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

Background and purpose: Ovarian cancer is one of the leading causes of cancer mortality in women. Despite
the increase in cases of this cancer, the current therapeutic strategy is not effective. 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.
Experimental approach: 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.
Findings / Results: 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 combination 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.
Conclusion and implications: 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