Induction of caspase-independent apoptotic-like cell death of mouse mammary tumor TA3Ha cells in vitro and reduction of their lethality in vivo by the novel chemotherapeutic agent GIT-27NO
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2010
Authors
Mijatović, SanjaMaksimović-Ivanić, Danijela
Timotijević, Gordana
Miljković, Djordje
Donia, Marco
Libra, Massimo
Coco, Marinella
McCubrey, James
Al-Abed, Yousef
Korac, Aleksandra
Stošić-Grujičić, Stanislava
Nicoletti, Ferdinando
Article (Published version)
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The new chemical entity GIT-27NO was created by the covalent linkage of a NO moiety to the antiinflammatory isoxazoline VGX-1027 The compound has been shown to possess powerful anticancer effects both in vitro and in vivo However, its effects on nonsolid and metastatic forms of tumors have not yet been investigated We have studied the effects of GIT-27NO on the highly invasive mouse mammary TA3Ha cell line in vitro and in vivo In contrast to the conventional exogenous NO donor sodium nitroprusside, GIT-27NO successfully enhanced intracellular NO concentration in TA3Ha cells Intracellular accumulation of NO was followed by marked decrease in TA3Ha cell viability accompanied by typical apoptotic features Interestingly, inverted membrane phosphatidylserine residues. reduced volume of nucleus, condensed chromatin, and terminal fragmentation of DNA were associated with inhibited caspase-3 activity and transcription of the genes encoding caspase-3, -8, and -9 In parallel, GIT-27NO rapidly bu...t transiently prevented the loss of p53 through phosphorylation on Ser 20 and provided the necessary signals tor the execution of downstream processes without p53 de novo synthesis The caspase-independent apoptotic-like death process triggered by GIT-27NO could be mediated by markedly down-regulated expression of the antiapoptotic Bcl-2 molecule observed in TA3Ha cells exposed to GIT-27NO In agreement with these in vitro data, GIT-27NO efficiently suppressed the growth of the ascites form and associated-lethality of tumor induced by TA3Ha cells in mice
Keywords:
TA3Ha / P53 / Nitric oxide / GTT-27NO / Free radicals / Caspases / Breast cancer / Bcl-2 / ApoptosisSource:
Free Radical Biology and Medicine, 2010, 48, 8, 1090-1099Publisher:
- Elsevier Science Inc, New York
Funding / projects:
- Fiziološka i farmakološka modulacija imunoinflamatornih i malignih bolesti (RS-MESTD-MPN2006-2010-143029)
DOI: 10.1016/j.freeradbiomed.2010.01.026
ISSN: 0891-5849
PubMed: 20114073
WoS: 000276448400011
Scopus: 2-s2.0-77950517076
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Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Mijatović, Sanja AU - Maksimović-Ivanić, Danijela AU - Timotijević, Gordana AU - Miljković, Djordje AU - Donia, Marco AU - Libra, Massimo AU - Coco, Marinella AU - McCubrey, James AU - Al-Abed, Yousef AU - Korac, Aleksandra AU - Stošić-Grujičić, Stanislava AU - Nicoletti, Ferdinando PY - 2010 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/434 AB - The new chemical entity GIT-27NO was created by the covalent linkage of a NO moiety to the antiinflammatory isoxazoline VGX-1027 The compound has been shown to possess powerful anticancer effects both in vitro and in vivo However, its effects on nonsolid and metastatic forms of tumors have not yet been investigated We have studied the effects of GIT-27NO on the highly invasive mouse mammary TA3Ha cell line in vitro and in vivo In contrast to the conventional exogenous NO donor sodium nitroprusside, GIT-27NO successfully enhanced intracellular NO concentration in TA3Ha cells Intracellular accumulation of NO was followed by marked decrease in TA3Ha cell viability accompanied by typical apoptotic features Interestingly, inverted membrane phosphatidylserine residues. reduced volume of nucleus, condensed chromatin, and terminal fragmentation of DNA were associated with inhibited caspase-3 activity and transcription of the genes encoding caspase-3, -8, and -9 In parallel, GIT-27NO rapidly but transiently prevented the loss of p53 through phosphorylation on Ser 20 and provided the necessary signals tor the execution of downstream processes without p53 de novo synthesis The caspase-independent apoptotic-like death process triggered by GIT-27NO could be mediated by markedly down-regulated expression of the antiapoptotic Bcl-2 molecule observed in TA3Ha cells exposed to GIT-27NO In agreement with these in vitro data, GIT-27NO efficiently suppressed the growth of the ascites form and associated-lethality of tumor induced by TA3Ha cells in mice PB - Elsevier Science Inc, New York T2 - Free Radical Biology and Medicine T1 - Induction of caspase-independent apoptotic-like cell death of mouse mammary tumor TA3Ha cells in vitro and reduction of their lethality in vivo by the novel chemotherapeutic agent GIT-27NO EP - 1099 IS - 8 SP - 1090 VL - 48 DO - 10.1016/j.freeradbiomed.2010.01.026 ER -
@article{ author = "Mijatović, Sanja and Maksimović-Ivanić, Danijela and Timotijević, Gordana and Miljković, Djordje and Donia, Marco and Libra, Massimo and Coco, Marinella and McCubrey, James and Al-Abed, Yousef and Korac, Aleksandra and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando", year = "2010", abstract = "The new chemical entity GIT-27NO was created by the covalent linkage of a NO moiety to the antiinflammatory isoxazoline VGX-1027 The compound has been shown to possess powerful anticancer effects both in vitro and in vivo However, its effects on nonsolid and metastatic forms of tumors have not yet been investigated We have studied the effects of GIT-27NO on the highly invasive mouse mammary TA3Ha cell line in vitro and in vivo In contrast to the conventional exogenous NO donor sodium nitroprusside, GIT-27NO successfully enhanced intracellular NO concentration in TA3Ha cells Intracellular accumulation of NO was followed by marked decrease in TA3Ha cell viability accompanied by typical apoptotic features Interestingly, inverted membrane phosphatidylserine residues. reduced volume of nucleus, condensed chromatin, and terminal fragmentation of DNA were associated with inhibited caspase-3 activity and transcription of the genes encoding caspase-3, -8, and -9 In parallel, GIT-27NO rapidly but transiently prevented the loss of p53 through phosphorylation on Ser 20 and provided the necessary signals tor the execution of downstream processes without p53 de novo synthesis The caspase-independent apoptotic-like death process triggered by GIT-27NO could be mediated by markedly down-regulated expression of the antiapoptotic Bcl-2 molecule observed in TA3Ha cells exposed to GIT-27NO In agreement with these in vitro data, GIT-27NO efficiently suppressed the growth of the ascites form and associated-lethality of tumor induced by TA3Ha cells in mice", publisher = "Elsevier Science Inc, New York", journal = "Free Radical Biology and Medicine", title = "Induction of caspase-independent apoptotic-like cell death of mouse mammary tumor TA3Ha cells in vitro and reduction of their lethality in vivo by the novel chemotherapeutic agent GIT-27NO", pages = "1099-1090", number = "8", volume = "48", doi = "10.1016/j.freeradbiomed.2010.01.026" }
Mijatović, S., Maksimović-Ivanić, D., Timotijević, G., Miljković, D., Donia, M., Libra, M., Coco, M., McCubrey, J., Al-Abed, Y., Korac, A., Stošić-Grujičić, S.,& Nicoletti, F.. (2010). Induction of caspase-independent apoptotic-like cell death of mouse mammary tumor TA3Ha cells in vitro and reduction of their lethality in vivo by the novel chemotherapeutic agent GIT-27NO. in Free Radical Biology and Medicine Elsevier Science Inc, New York., 48(8), 1090-1099. https://doi.org/10.1016/j.freeradbiomed.2010.01.026
Mijatović S, Maksimović-Ivanić D, Timotijević G, Miljković D, Donia M, Libra M, Coco M, McCubrey J, Al-Abed Y, Korac A, Stošić-Grujičić S, Nicoletti F. Induction of caspase-independent apoptotic-like cell death of mouse mammary tumor TA3Ha cells in vitro and reduction of their lethality in vivo by the novel chemotherapeutic agent GIT-27NO. in Free Radical Biology and Medicine. 2010;48(8):1090-1099. doi:10.1016/j.freeradbiomed.2010.01.026 .
Mijatović, Sanja, Maksimović-Ivanić, Danijela, Timotijević, Gordana, Miljković, Djordje, Donia, Marco, Libra, Massimo, Coco, Marinella, McCubrey, James, Al-Abed, Yousef, Korac, Aleksandra, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, "Induction of caspase-independent apoptotic-like cell death of mouse mammary tumor TA3Ha cells in vitro and reduction of their lethality in vivo by the novel chemotherapeutic agent GIT-27NO" in Free Radical Biology and Medicine, 48, no. 8 (2010):1090-1099, https://doi.org/10.1016/j.freeradbiomed.2010.01.026 . .