Silencing of Mcl-1 overcomes resistance of melanoma cells against TRAIL-armed oncolytic adenovirus by enhancement of apoptosis.
Adenoviridae
/ genetics
Apoptosis
Apoptosis Regulatory Proteins
/ genetics
Cell Line, Tumor
Gene Expression Regulation, Neoplastic
Gene Silencing
Genetic Therapy
Humans
Melanoma
/ genetics
Myeloid Cell Leukemia Sequence 1 Protein
/ genetics
Necrosis
Oncolytic Virotherapy
Oncolytic Viruses
/ genetics
Skin Neoplasms
/ genetics
TNF-Related Apoptosis-Inducing Ligand
/ genetics
Apoptosis
Mcl-1
Melanoma
Oncolytic adenovirus
TRAIL
siRNA
Journal
Journal of molecular medicine (Berlin, Germany)
ISSN: 1432-1440
Titre abrégé: J Mol Med (Berl)
Pays: Germany
ID NLM: 9504370
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
26
10
2020
accepted:
20
04
2021
revised:
01
04
2021
pubmed:
25
5
2021
medline:
9
2
2022
entrez:
24
5
2021
Statut:
ppublish
Résumé
Arming of oncolytic viruses with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown as a viable approach to increase the antitumor efficacy in melanoma. However, melanoma cells may be partially or completely resistant to TRAIL or develop TRAIL resistance, thus counteracting the antitumor efficiency of TRAIL-armed oncolytic viruses. Recently, we found that TRAIL resistance in melanoma cells can be overcome by inhibition of antiapoptotic Bcl-2 protein myeloid cell leukemia 1 (Mcl-1). Here, we investigated whether the cytotoxicity of AdV-TRAIL, an oncolytic adenovirus, which expresses TRAIL after induction by doxycycline (Dox), can be improved in melanoma cells by silencing of Mcl-1. Two melanoma cell lines, the TRAIL-resistant MeWo and the TRAIL-sensitive Mel-HO were investigated. Treatment of both cell lines with AdV-TRAIL resulted in a decrease of cell viability, which was caused by an increase of apoptosis and necrosis. The proapoptotic effects were dependent on induction of TRAIL by Dox and were more pronounced in Mel-HO than in MeWo cells. SiRNA-mediated silencing of Mcl-1 resulted in a further significant decrease of cell viability and a further increase of apoptosis and necrosis in AdV-TRAIL-infected MeWo and Mel-HO cells. However, while in absolute terms, the effects were more pronounced in Mel-HO cells, in relative terms, they were stronger in MeWo cells. These results show that silencing of Mcl-1 represents a suitable approach to increase the cytotoxicity of a TRAIL-armed oncolytic adenovirus in melanoma cells. KEY MESSAGES: • Cytotoxicity of TRAIL-expressing adenovirus can be enhanced by silencing of Mcl-1. • The effect occurs in TRAIL-sensitive and TRAIL-resistant melanoma cells. • Increase of apoptosis is the main mechanism induced by Mcl-1 silencing.
Identifiants
pubmed: 34028599
doi: 10.1007/s00109-021-02081-3
pii: 10.1007/s00109-021-02081-3
pmc: PMC8367928
doi:
Substances chimiques
Apoptosis Regulatory Proteins
0
MCL1 protein, human
0
Myeloid Cell Leukemia Sequence 1 Protein
0
TNF-Related Apoptosis-Inducing Ligand
0
TNFSF10 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1279-1291Informations de copyright
© 2021. The Author(s).
Références
Int Immunol. 2019 Jul 13;31(7):465-475
pubmed: 30753483
Mol Ther Nucleic Acids. 2017 Sep 15;8:300-316
pubmed: 28918031
J Biol Chem. 2005 Mar 18;280(11):10491-500
pubmed: 15637055
J Cell Physiol. 2018 Nov;233(11):8482-8498
pubmed: 29797573
Cancer Res. 2009 Feb 15;69(4):1448-58
pubmed: 19190348
Nature. 2010 Feb 18;463(7283):899-905
pubmed: 20164920
Nat Commun. 2018 Dec 17;9(1):5341
pubmed: 30559424
J Invest Dermatol. 2005 Nov;125(5):1010-9
pubmed: 16297203
Nature. 2016 Oct 27;538(7626):477-482
pubmed: 27760111
Clin Cancer Res. 2006 Sep 1;12(17):5224-30
pubmed: 16951242
Nat Rev Mol Cell Biol. 2014 Jan;15(1):49-63
pubmed: 24355989
Cancers (Basel). 2019 May 11;11(5):
pubmed: 31083589
Eur J Cell Biol. 2014 Jan-Feb;93(1-2):42-8
pubmed: 24361324
Oncotarget. 2015 Dec 1;6(38):40667-79
pubmed: 26512779
Antiviral Res. 2010 Oct;88(1):86-94
pubmed: 20708037
Nat Rev Cancer. 2016 Feb;16(2):99-109
pubmed: 26822577
Hematol Oncol Clin North Am. 2021 Feb;35(1):99-109
pubmed: 33759776
Oncogene. 2007 May 17;26(23):3364-77
pubmed: 17160022
J Invest Dermatol. 2001 Aug;117(2):333-40
pubmed: 11511312
Biomed Pharmacother. 2018 Feb;98:566-576
pubmed: 29288972
Nat Med. 1999 Feb;5(2):157-63
pubmed: 9930862
Biochim Biophys Acta. 2006 Sep-Oct;1757(9-10):1371-87
pubmed: 16950166
Cancer Cell. 2006 May;9(5):351-65
pubmed: 16697956
Am J Clin Dermatol. 2021 May;22(3):301-314
pubmed: 33765322
Cancer Res. 2002 Aug 15;62(16):4663-70
pubmed: 12183423
Pigment Cell Res. 1995 Dec;8(6):307-13
pubmed: 8789739
Oncogene. 2003 Dec 11;22(57):9131-41
pubmed: 14668794
Mol Ther. 2010 Feb;18(2):243-50
pubmed: 19935777
Nat Protoc. 2006;1(3):1458-61
pubmed: 17406435
Hum Gene Ther. 2011 Apr;22(4):405-17
pubmed: 20977303
BMC Cancer. 2014 Feb 07;14:74
pubmed: 24507727
CA Cancer J Clin. 2017 Nov;67(6):472-492
pubmed: 29028110
Genes Dev. 2013 Jun 15;27(12):1365-77
pubmed: 23788623
Nature. 2003 Dec 11;426(6967):671-6
pubmed: 14668867
Science. 2009 Jul 17;325(5938):332-6
pubmed: 19498109
Immunity. 2000 Jun;12(6):611-20
pubmed: 10894161
Mol Carcinog. 2020 Nov;59(11):1256-1268
pubmed: 32885857
Cell Death Differ. 2003 Jan;10(1):76-100
pubmed: 12655297
Arch Ophthalmol. 2005 May;123(5):654-61
pubmed: 15883285
Nat Rev Drug Discov. 2012 Feb 01;11(2):109-24
pubmed: 22293567
Cancer Gene Ther. 2009 Jun;16(6):473-88
pubmed: 19197323
J Virol. 2004 Nov;78(22):12243-51
pubmed: 15507611
Immunity. 2013 Feb 21;38(2):209-23
pubmed: 23438821
PLoS One. 2012;7(1):e30821
pubmed: 22292048
Science. 2005 Feb 18;307(5712):1101-4
pubmed: 15718471
J Cell Mol Med. 2015 May;19(5):915-23
pubmed: 25683371