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.
Highlights
Human ovarian cancer is the most fatal cancer in the female reproductive system [1,2,3]
Since the concentration of Lactate dehydrogenase (LDH) released into the extracellular environment corresponds to the degree of cell membrane damage, we used the LDH release assay to determine the cytotoxicity of Solanum lyratum Thunb (SLT) (Figure 1(a))
The results demonstrated that over 1.0 μg/mL of SLT remarkably increased LDH leakage of A2780 and SKOV3 cells, which suggested that high concentration of SLT might be cytotoxic
Summary
Human ovarian cancer is the most fatal cancer in the female reproductive system [1,2,3]. The traditional treatment process is to remove the tumor to the maximum and combine the paclitaxel and platinum chemotherapy [4]. 70% of the patients initially respond well to the chemotherapy, while the emergence of drug resistance and side effects curb the benefits of currently available chemotherapy drugs [5], and the 5-year survival is still unsatisfactory [6,7,8]. Since few of these strategies can completely protect patients with ovarian cancer from recurrence and metastasis, new drugs are urgently needed. It is necessary to study the natural products systematically, clarify their antitumor effects, and understand their mechanism, so as to develop new therapeutic methods
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