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Hepatocellular carcinoma (HCC) has particularly high incidence rate in Asia and its resistance to the chemotherapeutic drugs and cell death make it intractable. Vaccinia virus (VV) is a potential vehicle and has been widely used in cancer therapy. SMAC/DIABLO is a critical factor in activating caspases and eliminating inhibition of IAPs when the programmed cell death is promoted. In this study, we constructed a tumor-targeted vaccinia virus carrying SMAC/DIABLO gene that was knocked in the region of viral thymidine kinase gene (VV-SMAC). Our results showed that VV-SMAC efficiently infected and destroyed HCC cells via triggering both caspase-dependent apoptosis and necroptosis with depletion of IAPs. Furthermore, ripoptosome, a prerequisite complex of necroptosis, was assembled and induced by VV-SMAC. In addition, the combination of VV-SMAC and vinblastine represented a synergistic effect on HCC cells. In summary, our data suggest that VV-SMAC is a potential candidate and combination of VV-SMAC and vinblastine may provide a new avenue in treatment of HCC.

Titel:	SMAC-armed vaccinia virus induces both apoptosis and necroptosis and synergizes the efficiency of vinblastine in HCC.
Autor/in / Beteiligte Person:	Pan, Q ; Huang, Y ; Chen, L ; Gu, J ; Zhou, X
Link:	Full Text Finder (Volltext)
Zeitschrift:	Human cell, Jg. 27 (2014-10-01), Heft 4, S. 162-71
Veröffentlichung:	2011- : Tokyo : Springer ; <i>Original Publication</i>: Tōkyō-to : Hito Saibō Kenkyūkai : Kanishobo, Shōwa 63-nen [1988]-, 2014
Medientyp:	academicJournal
ISSN:	1749-0774 (electronic)
DOI:	10.1007/s13577-014-0093-z
Schlagwort:	Apoptosis Regulatory Proteins Carcinoma, Hepatocellular drug therapy Cell Line, Tumor Drug Synergism Humans Liver Neoplasms drug therapy Necrosis Thymidine Kinase genetics Thymidine Kinase therapeutic use Vinblastine therapeutic use Antineoplastic Agents, Phytogenic pharmacology Apoptosis drug effects Carcinoma, Hepatocellular pathology Carcinoma, Hepatocellular virology Intracellular Signaling Peptides and Proteins Liver Neoplasms pathology Liver Neoplasms virology Mitochondrial Proteins Thymidine Kinase pharmacology Vaccinia virus enzymology Vaccinia virus genetics Vinblastine pharmacology
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Hum Cell] 2014 Oct; Vol. 27 (4), pp. 162-71. <i>Date of Electronic Publication: </i>2014 Apr 26. MeSH Terms: Intracellular Signaling Peptides and Proteins* ; Mitochondrial Proteins* ; Antineoplastic Agents, Phytogenic / pharmacology ; Apoptosis / drug effects ; Carcinoma, Hepatocellular / pathology ; Carcinoma, Hepatocellular / virology ; Liver Neoplasms / pathology ; Liver Neoplasms / virology ; Thymidine Kinase / pharmacology ; Vaccinia virus / enzymology ; Vaccinia virus / genetics ; Vinblastine / pharmacology ; Apoptosis Regulatory Proteins ; Carcinoma, Hepatocellular / drug therapy ; Cell Line, Tumor ; Drug Synergism ; Humans ; Liver Neoplasms / drug therapy ; Necrosis ; Thymidine Kinase / genetics ; Thymidine Kinase / therapeutic use ; Vinblastine / therapeutic use References: Nature. 2000 Aug 24;406(6798):855-62. (PMID: 10972280) ; Nat Med. 2002 Aug;8(8):808-15. (PMID: 12118245) ; Nat Med. 2005 Jul;11(7):725-30. (PMID: 16015365) ; J Exp Clin Cancer Res. 2008 Sep 26;27:48. (PMID: 18822137) ; Acta Biochim Biophys Sin (Shanghai). 2012 Sep;44(9):737-45. (PMID: 22842821) ; Acta Pharmacol Sin. 2007 Dec;28(12):1996-2004. (PMID: 18031615) ; Cell. 2011 Mar 4;144(5):646-74. (PMID: 21376230) ; Genes Dev. 1999 Feb 1;13(3):239-52. (PMID: 9990849) ; J Biol Chem. 2013 Dec 6;288(49):35500-10. (PMID: 24165128) ; Semin Hematol. 2009 Jan;46(1 Suppl 2):S26-32. (PMID: 19245931) ; Nature. 2011 Aug 31;477(7362):99-102. (PMID: 21886163) ; Cancer Res. 2006 Apr 15;66(8):4291-8. (PMID: 16618754) ; Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7544-9. (PMID: 9636186) ; EMBO J. 2001 Dec 3;20(23):6627-36. (PMID: 11726499) ; J Virol. 2009 Feb;83(4):1563-71. (PMID: 19073732) ; Mol Cell. 2011 Aug 5;43(3):323-5. (PMID: 21816342) ; Cancer Res. 2003 Mar 15;63(6):1317-24. (PMID: 12649193) ; Hepatology. 2008 Aug;48(2):497-507. (PMID: 18666224) ; Clin Cancer Res. 2011 Aug 15;17(16):5412-22. (PMID: 21676925) ; Arch Virol. 1996;141(3-4):663-9. (PMID: 8645102) ; J Biol Chem. 2004 Apr 23;279(17):16963-70. (PMID: 14960576) ; J Biol Chem. 2007 Aug 17;282(33):24131-45. (PMID: 17580304) ; Mol Cell. 2011 Aug 5;43(3):432-48. (PMID: 21737329) ; Trends Cell Biol. 1999 Aug;9(8):323-8. (PMID: 10407412) ; J Clin Invest. 2007 Nov;117(11):3350-8. (PMID: 17965776) ; Cell. 2009 Jun 12;137(6):1112-23. (PMID: 19524513) ; Nat Rev Cancer. 2009 Jan;9(1):64-71. (PMID: 19104515) ; J Natl Compr Canc Netw. 2008 Jul;6(6):536-64. (PMID: 18597709) ; Cell. 2000 Jan 7;100(1):57-70. (PMID: 10647931) ; Histochemistry. 1993 Sep;100(3):223-9. (PMID: 8244773) ; Nat Rev Cancer. 2004 Apr;4(4):253-65. (PMID: 15057285) ; Gastroenterology. 2004 Nov;127(5 Suppl 1):S5-S16. (PMID: 15508102) ; Nat Chem Biol. 2008 May;4(5):313-21. (PMID: 18408713) ; CA Cancer J Clin. 2013 Jan;63(1):11-30. (PMID: 23335087) Substance Nomenclature: 0 (Antineoplastic Agents, Phytogenic) ; 0 (Apoptosis Regulatory Proteins) ; 0 (DIABLO protein, human) ; 0 (Intracellular Signaling Peptides and Proteins) ; 0 (Mitochondrial Proteins) ; 5V9KLZ54CY (Vinblastine) ; EC 2.7.1.21 (Thymidine Kinase) Entry Date(s): Date Created: 20140429 Date Completed: 20150330 Latest Revision: 20230525 Update Code: 20231215

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SMAC-armed vaccinia virus induces both apoptosis and necroptosis and synergizes the efficiency of vinblastine in HCC.