Anti-ovarian cancer actions and pharmacological targets of plumbagin.

Ovarian cancer is a gynecological malignancy characterized with increasing death rate in the world. It is clinically reported that chemotherapy against ovarian cancer is still found with poor curative effect and potential side effect. Plumbagin is an emerging anti-cancer compound. Although some experimental findings of plumbagin anti-ovarian cancer activity are described, the pharmacological targets should be further explored. In this study, we aimed to investigate the underlying pharmacological activities and targets of plumbagin against ovarian cancer in vitro. As results, in silico docking analysis suggested plumbagin potently treating ovarian cancer through regulating pharmacological targets, including octamer-binding transcription factor 4 (OCT4) and Kruppel-like factor 4 (KLF4). The preliminary experimental data showed that plumbagin treatment inhibited cell growth and induced apoptosis in cancer cells. In addition, decreased mRNA expressions of intracellular OCT4, PCNA, and elevated KLF4 mRNA activation were detected in plumbagin-treated cancer cells. Furthermore, immunostaining determination showed reduced OCT4-positive cells and increased KLF4-positive cells were observed following plumbagin treatments. To sum up, our current findings have preliminarily showed the anti-ovarian cancer benefits of plumbagin, and the pharmacological targets may be identified as KLF4 and OCT4 pathway. Thus, we conclude that plumbagin may be a bioactive compound for ovarian cancer treatment.

Methyl helicterate inhibits hepatic stellate cell activation through downregulating the ERK1/2 signaling pathway.

The present study was to investigate the inhibitory effect of methyl helicterate (MH) on hepatic stellate cells (HSC-T6), primarily elucidating the underlying mechanism of MH against liver fibrosis. HSC-T6 cells were activated by platelet-derived growth factor (PDGF) stimulation, and then the effects of MH on cell viability, cytomembrane integrity, colony, migration, apoptosis, and cell cycle were detected. Moreover, the regulative mechanism of MH on HSCs was investigated by detecting the activation of the extracellular signal-regulated kinase (ERK1/2) signaling pathway. The results showed that MH significantly inhibited HSC-T6 cell viability and proliferation in a concentration-dependent manner. It notably promoted the release of lactate dehydrogenase, destroying cell membrane integrity. MH also markedly inhibited HSC-T6 cell clonogenicity and migration. Moreover, MH treatment significantly induced cell apoptosis and arrested cell cycle at the G2 phase. The further study showed that MH inhibited the expression of ERK1, ERK2, c-fos, c-myc, and Ets-1, blocking the ERK1/2 pathway. In conclusion, this study demonstrates that MH significantly inhibits HSC activation and promotes cell apoptosis via downregulation of the ERK1/2 signaling pathway.