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

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.

Active substances and molecular mechanisms of the anti-myocardial ischemia effects of Carthami flos by network pharmacology and in vitro experiments

“…The present study showed that CF treatment significantly decreased LDH and CK in H 2 O 2 -treated H9c2 cells. Cell cycle arrest has been reported to be closely related to apoptosis induction, and our present study found that CFE protected H9c2 cells from cell cycle arrest caused by H 2 O 2 [ 30 ].…”

“…Combined with the results of PPI and essential genes analysis of CFE against MI, we think the anti-apoptosis and anti-oxidative stress via Akt/Nrf2 signaling is the main potential molecular mechanisms of CF. In addition, ROS are an important index reflecting oxidative stress in cells, and overproduction of ROS can induce apoptosis in cells [ 30 , 31 ]. Interestingly, our results showed that CFE reduced the ROS levels in H9c2 cells induced by H 2 O 2 .…”

“…Interestingly, our results showed that CFE reduced the ROS levels in H9c2 cells induced by H 2 O 2 . Caspase-3 and Bcl-2 are two core proteins for controlling cell apoptosis [ 32 , 33 ], and Akt/Nrf2 signaling is a crucial pathway for controlling oxidative stress [ 30 , 34 ]. In the present study, similar to the network pharmacology prediction results, CF treatment downregulated the mRNA expression of caspase-3 but upregulated that of Bcl-2, Akt and Nrf2 in H 2 O 2 -treated H9c2 cells.…”

Magnesium-L-threonate exhibited a neuroprotective effect against oxidative stress damage in HT22 cells and Alzheimer’s disease mouse model

“…PI3K/Akt pathway is an important cellular pathway occupying a pivotal role in the mediation of cell apoptosis[ 34 ]. A recent study demonstrated that Rotundifuran-induced ROS production could lead to cell apoptosis via suppressing the PI3K/Akt pathway in the cervical cancer cell model[ 35 ]. Another study also showed that inhibition of apoptosis was correlated with the ROS-mediated PI3K/Akt pathway in a streptozotocin-treated INS-1 cell model[ 24 ].…”

An update of label-free protein target identification methods for natural active products

“…2'-Hydroxycinnamaldehyde, a natural product isolated from the stem bark of Cinnamomum cassia, was found to selectively inhibit STAT3 activity by directly binding to STAT3 using a pull-down assay, DARTS and CETSA experiments 51 . Using proteomics analysis and DARTS methods, cysteine-rich angiogenic inducer 61 (Cyr61) was identified as a potential target for rotundifuran, a natural product isolated from Vitex trifolia L , in cervical cancer cells 101 . In the process of screening NAPs that inhibit STAT3 using DARTS and CETSA methods, geranylnaringenin was found to reduce luciferase activity in a dose-dependent manner and then regulate STAT3 activity by interacting with SHP-2 54 .…”