In summary, our work demonstrates that parthenolide induces both extrinsic and intrinsic apoptosis via ER stress signaling pathway in human NSCLC cells (Figure 8). Moreover, parthenolide induces stronger ER stress and apoptosis in cancer stem-like cells which may account for its selective effect in apoptosis induction. #MM-102 purchase randurls[1|1|,|CHEM1|]# Collectively, this study provides important mechanistic insight into potential cancer treatment with parthenolide as well as our understanding for cancer stem cells. Acknowledgements This work was supported by grants from the National Natural Science Foundation of China (81000947, 31071215 and 30971479), the Shandong
Natural Science Foundation (JQ201007) and the Independent Innovation Foundation of Shandong University (IIFSDU2012TS010, IIFSDU2009JQ006 and 11200070613201). Electronic supplementary material Additional file 1: Figure S1: Parthenolide induces cell cycle arrest in NSCLC cell Cilengitide cell line lines.
A549 (A) and H1792 (B) cells were treated with different concentrations of PTL for 24 hours. After treatment, the cells were harvested for cell cycle assays. Figure S2. Cancer stem cell makers are up-regulated in A549/shCDH1 cells. The expression level of SOX2 and POU5F1 were detected in A549/shCtrl and A549/shCDH1 cells by Western Blot assay. (PPT 246 KB) References 1. Schinella GR, Giner RM, Recio MC, Mordujovich de Buschiazzo P, Rios JL, Manez S: Anti-inflammatory effects of South American Tanacetum vulgare. J Pharm Pharmacol 1998, 50:1069–1074.PubMedCrossRef
2. Kim IH, Kim SW, Kim SH, Lee SO, Lee ST, Kim DG, et al.: Parthenolide-induced apoptosis of hepatic stellate cells and anti-fibrotic effects in an in vivo rat model. Exp Mol Med 2012, 44:448–456.PubMedCrossRef 3. Liu J, Cai M, Xin Y, Wu Q, Org 27569 Ma J, Yang P, et al.: Parthenolide induces proliferation inhibition and apoptosis of pancreatic cancer cells in vitro. J Exp Clin Cancer Res 2010, 29:108.PubMedCrossRef 4. Wen J, You KR, Lee SY, Song CH, Kim DG: Oxidative stress-mediated apoptosis. The anticancer effect of the sesquiterpene lactone parthenolide. J Biol Chem 2002, 277:38954–38964.PubMedCrossRef 5. Zhang S, Ong CN, Shen HM: Critical roles of intracellular thiols and calcium in parthenolide-induced apoptosis in human colorectal cancer cells. Cancer Lett 2004, 208:143–153.PubMedCrossRef 6. Wang W, Adachi M, Kawamura R, Sakamoto H, Hayashi T, Ishida T, et al.: Parthenolide-induced apoptosis in multiple myeloma cells involves reactive oxygen species generation and cell sensitivity depends on catalase activity. Apoptosis 2006, 11:2225–2235.PubMedCrossRef 7. Guzman ML, Rossi RM, Neelakantan S, Li X, Corbett CA, Hassane DC, et al.: An orally bioavailable parthenolide analog selectively eradicates acute myelogenous leukemia stem and progenitor cells. Blood 2007, 110:4427–4435.PubMedCrossRef 8. Zhou J, Zhang H, Gu P, Bai J, Margolick JB, Zhang Y, et al.