Abstract
Cervical cancer is a common female malignant tumor that seriously threatens human health. This study explored the anticervical cancer effects and potential mechanisms of Rotundifuran (RTF), a natural product isolated from Vitex trifolia L. In this study, we found that RTF can suppress the proliferation of cervical cancer cell lines, including HeLa and SiHa cells (with the IC50 less than 10 μM), via induction of apoptosis in vitro, and the antitumor effect of RTF is further confirmed on the HeLa cell-inoculated xenograft model. In addition, our results proved that the antitumor effects of RTF might be related with the reactive oxygen species- (ROS-) induced mitochondrial-dependent apoptosis through MAPK and PI3K/Akt signal pathways. Using proteomics analysis and the drug affinity responsive target stability- (DARTS-) combined mass spectrometry (DARTS-MS), Cyr61 was indicated as a potential target for RTF in cervical cancer cells. Our present study would be beneficial for the development of RTF as a candidate for treatment of cervical cancer in the future.
Highlights
Cervical cancer is one of the most common malignancies in women and remains the leading cause of cancer deaths among women worldwide, posing a serious threat to women’s health
After preparation of adequate monomer of RTF, we further evaluated the cytotoxic effects of this compound on cervical cancer cell lines of HeLa and SiHa cells using CCK-8 assays
Previous literatures have confirmed that the G2/M cycle arrest could induce cell apoptosis [18]
Summary
Cervical cancer is one of the most common malignancies in women and remains the leading cause of cancer deaths among women worldwide, posing a serious threat to women’s health. Epidemiological investigation in 2018 estimated that more than 550,000 cases of cervical cancer were definitely diagnosed every year. According to the NCCN clinical practice guidelines in oncology (https://nycancer.com/nccn/), the first-line drugs for cervical cancer include cisplatin, taxol, and topotecan. These mentioned drugs would bring lots of serious toxicities or side-effects [3, 4]. Some new drugs such as biochemicals have been tried in recent years, it is still hard to treat some advanced or recurrent cervical cancer [5, 6]. Searching for more novel and alternative reliable remedies with less toxicity for treating cervical cancer is of importance and necessary
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