Signaling network of OSW‑1‑induced apoptosis and necroptosis in hepatocellular carcinoma

Jin,Jichun; Jin,Xinglin; Qian,Changshi; Ruan ,Yang; Jiang,Hao

doi:10.3892/mmr.2013.1366

Signaling network of OSW‑1‑induced apoptosis and necroptosis in hepatocellular carcinoma

Authors:
- Jichun Jin
- Xinglin Jin
- Changshi Qian
- Yang Ruan
- Hao Jiang
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Affiliations: Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Yanbian University, Yanji, Jilin 133000, P.R. China
Published online on: March 13, 2013 https://doi.org/10.3892/mmr.2013.1366
Pages: 1646-1650

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Abstract

The compound 3β, 16β, 17α‑trihydroxycholest‑5‑en‑22‑one 16‑O‑(2‑O‑4‑methoxybenzoyl‑β‑D‑xylopyranosyl)‑ (1→3)‑(2‑O‑acetyl‑α‑L‑arabinopyranoside (OSW‑1) is a member of the cholestane saponin family that was created in the bulbs of Ornithogalum saudersiae. OSW‑1 has previously been shown as cytotoxic against numerous types of malignant cells, however, its antitumoral mechanisms remain unclear. The present study aimed to examine the potential changes in the gene expression of a hepatocellular carcinoma (HCC) cell line (Hep3B) incubated with OSW‑1 in vitro. The results showed that OSW‑1 inhibited tumors through invasiveness, angiogenesis, cell polarity and cell adhesion (as shown by Roche NimbleGen gene expression analysis), in addition to inducing apoptosis through the mitochondrial pathway. This affected the expression of a number of core genes in a number of signaling pathways, including WNT, MAPK, VEGF and P53. To the best of our knowledge, the present study is the first to report that OSW‑1, as a molecular compound, induces necroptotic death in hepatocellular carcinoma (HCC).

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1	Kubo S, Mimaki Y, Terao M, Sashida Y, Nikaido T and Ohmoto T: Acylated cholestane glycosides from the bulbs of Ornithogalum saudersiae. Phytochemistry. 31:3969–3973. 1992. View Article : Google Scholar
2	Mimaki Y, Kuroda M, Kameyama A, Sashida Y, Hirano T and Oka K: Cholestane glycosides with potent cytostatic activities on various tumor cells from Ornithogalum saundersiae bulls. Bioorg Med Chem Lett. 7:633–636. 1997. View Article : Google Scholar
3	Zhou Y, Garcia-Prieto C, Carney DA, et al: OSW-1: a natural compound with potent anticancer activity and a novel mechanism of action. J Natl Cancer Inst. 97:1781–1785. 2005. View Article : Google Scholar : PubMed/NCBI
4	Cai FG, Xiao JS and Ye QF: Effects of ischemic preconditioning on cyclinD1 expression during early ischemic reperfusion in rats. World J Gastroenterol. 12:2936–2940. 2006.PubMed/NCBI
5	Kim EK and Choi EJ: Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta. 1802:396–405. 2010. View Article : Google Scholar : PubMed/NCBI
6	McKay MM and Morrison DK: Integrating signals from RTKs to ERK/MAPK. Oncogene. 26:3113–3121. 2007. View Article : Google Scholar : PubMed/NCBI
7	Ballif BA and Blenis J: Molecular mechanisms mediating mammalian mitogen-activated protein kinase (MAPK) kinase (MEK)-MAPK cell survival signals. Cell Growth Differ. 12:397–408. 2001.PubMed/NCBI
8	Bonni A, Brunet A, West AE, Datta SR, Takasu MA and Greenberg ME: Cell survival promoted by the Ras-MAPK signalling pathway by transcription-dependent and -independent mechanisms. Science. 286:1358–1362. 1999. View Article : Google Scholar : PubMed/NCBI
9	Zhu J, Xiong L, Yu B and Wu J: Apoptosis induced by a new member of saponin family is mediated through caspase-8-dependent cleavage of Bcl-2. Mol Pharmacol. 68:1831–1838. 2005.PubMed/NCBI
10	Porras A, Zuluaga S, Black E, et al: P38 alpha mitogen-activated protein kinase sensitizes cells to apoptosis induced by different stimuli. Mol Biol Cell. 15:922–933. 2004. View Article : Google Scholar
11	Grethe S and Pörn-Ares MI: p38 MAPK regulates phosphorylation of Bad via PP2A-dependent suppression of the MEK1/2-ERK1/2 survival pathway in TNF-alpha induced endothelial apoptosis. Cell Signal. 18:531–540. 2006. View Article : Google Scholar
12	Zhong Q, Zhou Y, Ye W, Cai T, Zhang X and Deng DY: Hypoxia-inducible factor 1-α-AA-modified bone marrow stem cells protect PC12 cells from hypoxia-induced apoptosis, partially through VEGF/PI3K/Akt/FoxO1 pathway. Stem Cells Dev. 21:2703–2717. 2012.
13	Adya R, Tan BK, Punn A, Chen J and Randeva HS: Visfatin induces human endothelial VEGF and MMP-2/9 production via MAPK and PI3K/Akt signalling pathways: novel insights into visfatin-induced angiogenesis. Cardiovasc Res. 78:356–365. 2008. View Article : Google Scholar
14	Chiang IT, Liu YC, Wang WH, et al: Sorafenib inhibits TPA-induced MMP-9 and VEGF expression via suppression of ERK/NF-κB pathway in hepatocellular carcinoma cells. In Vivo. 26:671–681. 2012.PubMed/NCBI
15	Villunger A, Michalak EM, Coultas L, et al: p53- and drug-induced apoptotic responses mediated by BH3-only proteins puma and noxa. Science. 302:1036–1038. 2003. View Article : Google Scholar : PubMed/NCBI
16	Park SY, Jeong MS and Jang SB: In vitro binding properties of tumor suppressor p53 with PUMA and NOXA. Biochem Biophys Res Commun. 420:350–356. 2012. View Article : Google Scholar : PubMed/NCBI
17	Huang DC and Strasser A: BH3-only proteins - essential initiators of apoptotic cell death. Cell. 103:839–842. 2000. View Article : Google Scholar : PubMed/NCBI
18	Michalak EM, Villunger A, Adams JM and Strasser A: In several cell types tumour suppressor p53 induces apoptosis largely via Puma but Noxa can contribute. Cell Death Differ. 15:1019–1029. 2008. View Article : Google Scholar : PubMed/NCBI
19	Vaseva AV and Moll UM: The mitochondrial p53 pathway. Biochim Biophys Acta. 1787:414–420. 2009. View Article : Google Scholar : PubMed/NCBI
20	Leu JI, Dumont P, Hafey M, Murphy ME and George DL: Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcl1 complex. Nat Cell Biol. 6:443–450. 2004. View Article : Google Scholar : PubMed/NCBI
21	Gogvadze V, Orrenius S and Zhivotovsky B: Mitochondria as targets for cancer chemotherapy. Semin Cancer Biol. 19:57–66. 2009. View Article : Google Scholar : PubMed/NCBI
22	Nagata S and Golstein P: The Fas death factor. Science. 267:1449–1456. 1995. View Article : Google Scholar
23	O’Connor L, Harris AW and Strasser A: CD95 (Fas/APO-1) and p53 signal apoptosis independently in diverse cell types. Cancer Res. 60:1217–1220. 2000.PubMed/NCBI
24	Vandenabeele P, Galluzzi L, Vanden Berghe T and Kroemer G: Molecular mechanisms of necroptosis: an ordered cellular explosion. Nat Rev Mol Cell Biol. 11:700–714. 2010. View Article : Google Scholar : PubMed/NCBI
25	Han W, Li L, Qiu S, et al: Shikonin circumvents cancer drug resistance by induction of a necroptotic death. Mol Cancer Ther. 6:1641–1649. 2007. View Article : Google Scholar : PubMed/NCBI
26	Burgett AW, Poulsen TB, Wangkanont K, et al: Natural products reveal cancer cell dependence on oxysterol-binding proteins. Nat Chem Biol. 7:639–647. 2011. View Article : Google Scholar : PubMed/NCBI
27	Hitomi J, Christofferson DE, Ng A, Yao J, Degterev A, Xavier RJ and Yuan J: Identification of a molecular signalling network that regulates a cellular necrotic cell death pathway. Cell. 135:1311–1323. 2008. View Article : Google Scholar : PubMed/NCBI