Hexane fraction of Pluchea indica root extract inhibits proliferation and induces autophagy in human glioblastoma cells.

Pluchea indica (L.) Less. is a perennial plant known for its versatile uses in traditional medicine. Previous findings have shown that the extracts of Pluchea indica possess significant anti-inflammatory, anti-ulcer and anti-tuberculosis activity. The aim of this study was to demonstrate the anticancer activity of the hexane fraction of P. indica root extract (H-PIRE) in human glioblastoma cells using flow cytometric and western blot analysis. The results shoewd that, H-PIRE suppressed the growth of glioblastoma cells in a dose-dependent manner. H-PIRE treatment markedly decreased the population of cells in S and G2/M phases. The significant upregulation of acidic vesicular organelle (AVO) was detected during H-PIRE treatment. The expression levels of microtubule-associated light chain 3-II (LC3-II) protein, phosphorylated JNK and phosphorylated p38 were significantly increased, confirming the occurrence of autophagy during the process. Finally, the combination treatment of H-PIRE and LY294002, a pan PI3K inhibitor, further decreased cell viability, suggesting an additive anticancer effect. Taken together, our results suggest that H-PIRE suppresses the proliferation of glioblastoma cells by inducing cell cycle arrest and autophagy.

Ethanolic Extracts of Pluchea indica Induce Apoptosis and Antiproliferation Effects in Human Nasopharyngeal Carcinoma Cells.

Pluchea indica is used in traditional medicine for the treatment of lumbago, ulcer, tuberculosis and inflammation. The anti-cancer activities and the underlying molecular mechanisms of the ethanolic extracts of P. indica root (PIRE) were characterized in the present study. PIRE strongly inhibited the viability of the human nasopharyngeal carcinoma cells (NPC-TW 01 and NPC-TW 04) in a time- and dose-dependent manner. Migration of cancer cells was also suppressed by PIRE. In addition, PIRE significantly increased the occurrence of the cells in sub-G1 phase and the extent of DNA fragmentation in a dose-dependent manner, which indicates that PIRE significantly increased apoptosis in NPC cells. The apoptotic process triggered by PIRE involved up-regulation of pro-apoptotic Bax protein and down-regulation of anti-apoptotic Bcl-2 protein, consequently increasing the ratios of Bax/Bcl-2 protein levels. Moreover, the p53 protein was up-regulated by PIRE in a concentration-dependent manner. Therefore, PIRE could induce the apoptosis-signaling pathway in NPC cells by activation of p53 and by regulation of apoptosis-related proteins.

Heat shock induces expression of OSTC/DC2, a novel subunit of oligosaccharyltransferase, in vitro and in vivo.

Mammalian oligosaccharyltransferase complex subunit OSTC/DC2 protein has recently been shown to be a new subunit of the oligosaccharyltransferase; however, its physiological role is still unclear. Here, we report the expression pattern of OSTC/DC2 protein in the context of heat shock stress. Its upregulation was detected both in cells treated with heat shock in vitro and in an animal model of heat shock in vivo. Northern blot analysis indicated that OSTC/DC2 mRNA is ubiquitously expressed in various human tissues, with abundant expression in the placenta and liver. The temporal changes of OSTC/DC2 protein expression following acute heat shock in human malignant glioblastoma cell line U87MG and mice were analyzed by Western blot assay. In general, expression of OSTC/DC2 protein was elevated after heat shock; however, the time courses of the change of OSTC/DC2 protein expression varied in different tissues. In the cerebellum, heat shock induction of OSTC/DC2 protein and activation of AKT, a key regulator of stress response, followed a similar time course. These results suggest that the upregulation of OSTC/DC2, a novel component of the oligosaccharyltransferase complex, is part of the mammalian heat shock response.

Crude aqueous extracts of Pluchea indica (L.) Less. inhibit proliferation and migration of cancer cells through induction of p53-dependent cell death.

BACKGROUND: Pluchea indica (L.) Less. (Asteraceae) is a perennial shrub plant with anti-inflammatory and antioxidant medicinal properties. However, the anti-cancer properties of its aqueous extracts have not been studied. The aim of this study was to investigate the anti-proliferation, anti-migration, and pro-apoptotic properties of crude aqueous extracts of P. indica leaf and root on human malignant glioma cancer cells and human cervical cancer cells, and the underlying molecular mechanism. METHODS: GBM8401 human glioma cells and HeLa cervical carcinoma cells were treated with various concentrations of crude aqueous extracts of P. indica leaf and root and cancer cell proliferation and viability were measured by cell growth curves, trypan blue exclusions, and the tetrazolium reduction assay. Effects of the crude aqueous extracts on focus formation, migration, and apoptosis of cancer cells were studied as well. The molecular mechanism that contributed to the anti-cancer activities of crude aqueous extracts of P. indica root was also examined using Western blotting analysis. RESULTS: Crude aqueous extracts of P. indica leaf and root suppressed proliferation, viability, and migration of GBM8401 and HeLa cells. Treatment with crude aqueous extracts of P. indica leaf and root for 48 hours resulted in a significant 75% and 70% inhibition on proliferation and viability of GBM8401 and HeLa cancer cells, respectively. Crude aqueous extracts of P. indica root inhibited focus formation and promoted apoptosis of HeLa cells. It was found that phosphorylated-p53 and p21 were induced in GBM8401 and HeLa cells treated with crude aqueous extracts of P. indica root. Expression of phosphorylated-AKT was decreased in HeLa cells treated with crude aqueous extracts of P. indica root. CONCLUSION: The in vitro anti-cancer effects of crude aqueous extracts of P. indica leaf and root indicate that it has sufficient potential to warrant further examination and development as a new anti-cancer agent.