Ethanol Extracts of Solanum lyratum Thunb Regulate Ovarian Cancer Cell Proliferation, Apoptosis, and Epithelial-to-Mesenchymal Transition (EMT) via the ROS-Mediated p53 Pathway

Abstract

Ovarian cancer is a type of common gynecological tumors with high incidence and poor survival. The anticancer effects of the traditional Chinese medicine Solanum lyratum Thunb (SLT) have been intensively investigated in various cancers but in ovarian cancer is rare. The current study is aimed at investigating the effect of SLT on ovarian cancer cells. Lactate dehydrogenase (LDH) and MTT assays indicated that SLT concentrations of 0.25 and 0.5 μg/mL were not cytotoxic and had significant inhibitory effects on the cell viabilities of A2780 and SKOV3 cells, hence were used for subsequent experiments. Flow cytometric and western blot analysis revealed that SLT effectively suppressed ovarian cancer cell proliferation via inducing cell cycle arrest and increasing apoptosis. Cell cycle and apoptosis-related protein expressions were also regulated in SLT-treated cells. Moreover, DCFH-DA and western blot assays demonstrated that SLT enhanced ROS accumulation and subsequently activated the p53 signaling pathway. However, SLT-regulated ovarian cancer cell proliferation, apoptosis, migration, invasion, and EMT were significantly reversed by an ROS inhibitor (NAC, N-acetyl-L-cysteine). Furthermore, A2780 and SKOV3 cells cocultured with M0 macrophages showed that SLT activated the polarization of M0 macrophages to M1 macrophages and inhibited the polarization to M2 macrophages, with the increased percentage of CD86+ cells and decreased percentage of CD206+ cells were detected. In summary, this study illustrated the anticancer effects of SLT on ovarian cancer cells, suggesting that SLT may have the potential to provide basic evidence for the discovery of antiovarian cancer agents.

LCS-1 inhibition of superoxide dismutase 1 induces ROS-dependent death of glioma cells and degradates PARP and BRCA1

“…It has been reported that ROS activates P53 signaling pathway ( 24 – 26 ). To determine whether LCS-1-induced cell death is associated with P53 activation, P53-targeted genes including Bcl-2, MDM2, Noxa were measured by qRT-PCR.…”

“…Multiple evidences show that ROS induced by various factors elicit cell differentiation, cell death, and inhibit tumor growth via P53 pathway ( 24 – 26 ). In this study, we found that LCS-1 has less effect on P53-targeted genes, indicating that LCS-1 did not activate P53.…”

Bisphenol A Promotes the Progression of Colon Cancer Through Dual-Targeting of NADPH Oxidase and Mitochondrial Electron-Transport Chain to Produce ROS and Activating HIF-1α/VEGF/PI3K/AKT Axis

“…Note that the enhanced tumor cell migration might not be completely related to EMT and was probably caused by actin and sometimes by movement protein change ( 34 ). According to the literature, the production amount of ROS was accumulated rapidly under the condition of BPA stimulation, but the increase in ROS might activate the downstream signal pathway to inhibit the occurrence of EMT ( 43 ). The exact mechanism remains unclear and requires further research.…”

A Network Pharmacology Study to Uncover the Mechanism of FDY003 for Ovarian Cancer Treatment

“…The programmed deathligand 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway, which regulates antitumor immune response, is a prognostic indicator for the survival of patients with OC 103 . Genetic mutations and improper functional modulation of the p53 pathway may result in metastasis, EMT, proliferation, and increased survival and motility of OC cells and tumors; these are key mechanisms in the incidence, prognosis, and disease progression [104][105][106][107][108][109][110] .…”