The Cyr61 Is a Potential Target for Rotundifuran, a Natural Labdane-Type Diterpene from Vitex trifolia L., to Trigger Apoptosis of Cervical Cancer Cells.

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.

Isorhamnetin: A review of pharmacological effects.

Isorhamnetin is one of the most important active ingredients in the fruits of Hippophae rhamnoides L. and the leaves of Ginkgo biloba L., which possesses extensive pharmacological activities. At present, there have been numerous investigations on isorhamnetin, which has the effects of cardiovascular and cerebrovascular protection, anti-tumor, anti-inflammatory, anti-oxidation, organ protection, prevention of obesity, etc. The related mechanisms involve the regulation of PI3K/AKT/PKB, NF-κB, MAPK and other signaling pathways as well as the expression of related cytokines and kinases. Isorhamnetin has a high value of development and application. However, the investigations on its mechanism of action are limited and lack of detailed scientific validation. The manuscript reviewed the pharmacological effects of isorhamnetin and related mechanisms of action for the development of its medicinal properties further.