MicroRNA-374b inhibits cervical cancer cell proliferation and induces apoptosis through the p38/ERK signaling pathway by binding to JAM-2.

Cervical cancer (CC) remains a highly prevalent cancer and mortality globally among women globally. The aim of the present study was to assess the ability of miR-374b to regulate CC cells through JAM-2, whilst exploring whether the underlying mechanism and its relation to the p38/ERK signaling pathway. During the study, microRNA-374b (miR-374b) was observed to have been expressed at a low level among CC tissues. Hence, a series of miR-374b mimics, miR-374b inhibitors, siRNA against JAM-2, SB202190 (an inhibitor for p38), and PD98059 (an inhibitor for ERK) were introduced to treat CC Siha cells and normal cervical Ect1/E6E7 cells. MTT, flow cytometry, scratch test, and transwell assays were applied to determine cell viability, apoptosis, migration, and invasion. The inhibitory role of the p38/ERK signaling pathway was observed in the CC cells treated with miR-374b mimics or siRNA against JAM-2. miR-374b mimic exposure was found to reduce cell viability, migration, and invasion, but induce apoptosis. MiR-374b inhibitor exposure was observed to have induced effects on the CC cells in a contrary manner to those induced by that of the miR-374b mimics. The key findings of the study demonstrated that miR-374b significantly inhibits cell proliferation, migration, and invasion through the blockade of the p38/ERK signaling pathway activation, as well as negatively binding to JAM-2, highlighting its potential as a therapeutic target for CC.

Dietary flavonoid tangeretin induces reprogramming of epithelial to mesenchymal transition in prostate cancer cells by targeting the PI3K/Akt/mTOR signaling pathway.

Tangeretin, a natural polymethoxyflavone present in the peel of citrus fruits is known to exhibit anticancer properties against a variety of carcinomas. Previous experimental evidence suggests that lifestyle and dietary habits affect the risk of prostate cancer to a certain extent. As the effect of tangeretin on prostate cancer is unexplored, the present study investigated the effect of tangeretin on androgen-insensitive PC-3 cells and androgen-sensitive LNCaP cells. Tangeretin reduced the cell viability of PC-3 cells in a dose- and time-dependent manner, with the half-maximal inhibitory concentration (IC50) observed at 75 µM dose following 72 h of incubation, while in LNCaP cells, the IC50 was identified to be ~65 µM. Expression levels of the mesenchymal proteins including vimentin, cluster of differentiation 44 and Neural cadherin in PC-3 cells were reduced by tangeretin treatment, whereas those of the epithelial proteins, including Epithelial cadherin and cytokeratin-19 were upregulated. Treatment of PC-3 cells also resulted in the downregulation of the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway. Therefore, it may be concluded that tangeretin induces reprogramming of epithelial-mesenchymal transition in PC-3 cells by targeting the PI3K/Akt/mTOR signaling pathway.

Metabolic behavior prediction of pazopanib by cytochrome P450 (CYP) 3A4 by molecular docking.

Metabolism-mediated drug adverse effects (e.g., drug-drug interaction, bioactivation, etc.) strongly limit the utilization of clinical drugs. The present study aims to predict the metabolic capability of cytochrome P450 (CYP) 3A4 toward pazopanib which is an excellent drug exhibiting therapeutic role toward various cancers especially for ovarian cancer. Pazopanib can be well docked into the activity cavity of CYP3A4, and the interaction structure in pazopanib was methyl group located besides nitrogen in the five-membered ring. The distance between the hydrogen atom in methyl group and active center is 3.64 Å. The interaction amino acid is Glu374. Furthermore, both pazopanib and ketoconazole were docked into the activity cavity of CYP3A4 to compare their binding potential. The distance between ketoconazole and activity center (2.10 Å) is closer than the distance between pazopanib and activity center of CYP3A4, indicating the easy influence of CYP3A4 inhibitor toward the metabolism of pazopanib. All these data were helpful for the clinical application of pazopanib, and R&D of other tinib drug candidates as new anti-tumor drugs.