Celastrol Inhibits the Growth of Ovarian Cancer Cells in vitro and in vivo.

Celastrol is a natural triterpene isolated from the Chinese plant Thunder God Vine with potent antitumor activity. However, the effect of celastrol on the growth of ovarian cancer cells in vitro and in vivo is still unclear. In this study, we found that celastrol induced cell growth inhibition, cell cycle arrest in G2/M phase and apoptosis with the increased intracellular reactive oxygen species (ROS) accumulation in ovarian cancer cells. Pretreatment with ROS scavenger N-acetyl-cysteine totally blocked the apoptosis induced by celastrol. Additionally, celastrol inhibited the growth of ovarian cancer xenografts in nude mice. Altogether, these findings suggest celastrol is a potential therapeutic agent for treating ovarian cancer.

Survivin Promotes Piperlongumine Resistance in Ovarian Cancer.

Ovarian cancer is one of the most fatal female malignancies while targeting apoptosis is critical for improving ovarian cancer patients' lives. Survivin is regarded as the most robust anti-apoptosis protein, and its overexpression in ovarian cancer is related to poor survival and apoptosis resistance. Piperlongumine (PL) extracted from peppers is defined as an active alkaloid/amide and exhibits a broad spectrum of antitumor effects. Here, we demonstrate that PL induces the rapid depletion of survivin protein levels via reactive oxygen species (ROS)-mediated proteasome-dependent pathway in vitro, while exerting a remarkable inhibitory influence on the proliferation of ovarian cancer cells. Overexpression of survivin raises the survival rate of ovarian cancer cells to PL. Moreover, PL inhibits ovarian cancer cells xenograft tumor growth and downregulates survivin in vivo. Our findings reveal a previously unrecognized mechanism of PL in suppressing survivin expression as well as survivin promotes piperlongumine resistance in ovarian cancer and suggest that ROS-mediated proteasome-dependent pathway can be exploited to overcome apoptosis resistance triggered by aberrant expression of survivin.

Erastin Reverses ABCB1-Mediated Docetaxel Resistance in Ovarian Cancer.

Overexpression of drug efflux transport ABCB1 is correlated with multidrug resistance (MDR) among cancer cells. Upregulation of ABCB1 accounts for the recurrence of resistance to docetaxel therapy in ovarian cancer with poor survival. Erastin is a novel and specific small molecule that targets SLC7A11 to induce ferroptosis. In the present research, we explored the synergistic effect of erastin and docetaxel in ovarian cancer. We confirmed that the co-delivery of erastin with docetaxel significantly decreased cell viability, promoted cell apoptosis, and induced cell cycle arrest at G2/M in ovarian cancer cells with ABCB1 overexpression. Mechanistically, erastin dominantly elevated the intracellular ABCB1 substrate levels by restricting the drug-efflux activity of ABCB1 without alteration of the expression of ABCB1. Consequently, erastin can reverse ABCB1-mediated docetaxel resistance in ovarian cancer, revealing that the combination of erastin and docetaxel may potentially offer an effective administration for chemo-resistant patients suffering from ovarian cancers.