Abstract
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.
Highlights
Ovarian cancer is the most fatal female reproductive tract cancer and the seventh most common cancer among women all over the world [1]
Because of the apoptotic effect of PL induced in ovarian cancer cells, we explored the negative regulation of PL on survivin expression
These evidences manifested that PL induces the reduction of survivin ovarian cancer cells in vitro, which may contribute to its apoptotic effect
Summary
Ovarian cancer is the most fatal female reproductive tract cancer and the seventh most common cancer among women all over the world [1]. It was evaluated that 22,240 ovarian cancer cases would be diagnosed while concurrently 14,070 women would succumb to the disease in 2018 [2]. Between 1976 and 2015, owing to effective approaches to the clinical treatment, including aggressive cytoreductive surgery followed by system chemotherapy, the mortality rate of ovarian cancer declined by 33% [2]. Despite the markable achievement of ovarian cancer during the last decade, the prognosis for women with advanced disease remains poor and chemoresistance appears to be a significant obstacle constraining the clinical application [3]. One of the inhibitor of apoptosis proteins family (IAP) firstly found in 1997, may accelerate the progress of cancer via promoting the insurgence of mutations as well as inducing resistance to chemotherapy [4]. Survivin could be a promising target for apoptosis-based treatment in ovarian cancer therapy [9]
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