Therapeutic Potential of Nitric Oxide-Modified Drugs in Colon Cancer Cells
Samo za registrovane korisnike
2012
Autori
Mojić, MarijaMijatović, Sanja
Maksimović-Ivanić, Danijela
Miljković, Djordje
Stošić-Grujičić, Stanislava
Stanković, Marija
Mangano, Katia
Travali, Salvatore
Donia, Marco
Fagone, Paolo
Zocca, Mai-Britt
Al-Abed, Yousef
McCubrey, James A.
Nicoletti, Ferdinando
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
We have examined the influence of the nitric oxide (NO)modified anti-inflammatory drug (S, R)-3-phenyl-4,5-dihydro-5-isoxasole acetic acid (VGX-1027) named GIT-27NO or the NO-modified antiviral drug saquinavir (Saq) named Saq-NO on two colon cancer cell lines, mouse CT26CL25 and human HCT116. The effects of the drugs on cell viability, apoptosis, proliferation, and metastatic potential were analyzed. The release of NO and oxygen and nitrogen species was also determined. The efficacy of the drugs was evaluated in vivo in BALB/c mice injected with CT26CL25 cells. Both agents suppressed the growth of colon cancer cells in vitro and reduced tumor volume in syngeneic BALB/c mice. However, their mechanisms of action were different because GIT-27NO released larger amounts of nitrite than Saq-NO in cell cultures and its antitumor action depended on the intracellular NO release inside the cells. On the contrary, Saq-NO released barely detectable amounts of NO and its antitumor action was NO-ind...ependent. In fact, cotreatment with an NO-peroxynitrite scavenger revealed that GIT-27NO but not Saq-NO acts through peroxynitrite-mediated cell destruction. At the cellular level, GIT-27NO prevalently induced proapoptotic signals followed by caspase-dependent apoptosis. In contrast, Saq-NO blocked cell proliferation, changed the adhesive, migratory, and invasive properties of the cells, and decreased metastatic potential in vivo. In conclusion, differences in NO release and oxidative stress generation between GIT-27NO and Saq-NO resulted in different mechanisms that caused cell death.
Izvor:
Molecular Pharmacology, 2012, 82, 4, 700-710Izdavač:
- Amer Soc Pharmacology Experimental Therapeutics, Bethesda
Finansiranje / projekti:
- Molekularni mehanizmi fiziološke i farmakološke kontrole inflamacije i kancera (RS-MESTD-Basic Research (BR or ON)-173013)
DOI: 10.1124/mol.112.077842
ISSN: 0026-895X
PubMed: 22798453
WoS: 000309509900015
Scopus: 2-s2.0-84866853268
Institucija/grupa
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Mojić, Marija AU - Mijatović, Sanja AU - Maksimović-Ivanić, Danijela AU - Miljković, Djordje AU - Stošić-Grujičić, Stanislava AU - Stanković, Marija AU - Mangano, Katia AU - Travali, Salvatore AU - Donia, Marco AU - Fagone, Paolo AU - Zocca, Mai-Britt AU - Al-Abed, Yousef AU - McCubrey, James A. AU - Nicoletti, Ferdinando PY - 2012 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/548 AB - We have examined the influence of the nitric oxide (NO)modified anti-inflammatory drug (S, R)-3-phenyl-4,5-dihydro-5-isoxasole acetic acid (VGX-1027) named GIT-27NO or the NO-modified antiviral drug saquinavir (Saq) named Saq-NO on two colon cancer cell lines, mouse CT26CL25 and human HCT116. The effects of the drugs on cell viability, apoptosis, proliferation, and metastatic potential were analyzed. The release of NO and oxygen and nitrogen species was also determined. The efficacy of the drugs was evaluated in vivo in BALB/c mice injected with CT26CL25 cells. Both agents suppressed the growth of colon cancer cells in vitro and reduced tumor volume in syngeneic BALB/c mice. However, their mechanisms of action were different because GIT-27NO released larger amounts of nitrite than Saq-NO in cell cultures and its antitumor action depended on the intracellular NO release inside the cells. On the contrary, Saq-NO released barely detectable amounts of NO and its antitumor action was NO-independent. In fact, cotreatment with an NO-peroxynitrite scavenger revealed that GIT-27NO but not Saq-NO acts through peroxynitrite-mediated cell destruction. At the cellular level, GIT-27NO prevalently induced proapoptotic signals followed by caspase-dependent apoptosis. In contrast, Saq-NO blocked cell proliferation, changed the adhesive, migratory, and invasive properties of the cells, and decreased metastatic potential in vivo. In conclusion, differences in NO release and oxidative stress generation between GIT-27NO and Saq-NO resulted in different mechanisms that caused cell death. PB - Amer Soc Pharmacology Experimental Therapeutics, Bethesda T2 - Molecular Pharmacology T1 - Therapeutic Potential of Nitric Oxide-Modified Drugs in Colon Cancer Cells EP - 710 IS - 4 SP - 700 VL - 82 DO - 10.1124/mol.112.077842 ER -
@article{ author = "Mojić, Marija and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Miljković, Djordje and Stošić-Grujičić, Stanislava and Stanković, Marija and Mangano, Katia and Travali, Salvatore and Donia, Marco and Fagone, Paolo and Zocca, Mai-Britt and Al-Abed, Yousef and McCubrey, James A. and Nicoletti, Ferdinando", year = "2012", abstract = "We have examined the influence of the nitric oxide (NO)modified anti-inflammatory drug (S, R)-3-phenyl-4,5-dihydro-5-isoxasole acetic acid (VGX-1027) named GIT-27NO or the NO-modified antiviral drug saquinavir (Saq) named Saq-NO on two colon cancer cell lines, mouse CT26CL25 and human HCT116. The effects of the drugs on cell viability, apoptosis, proliferation, and metastatic potential were analyzed. The release of NO and oxygen and nitrogen species was also determined. The efficacy of the drugs was evaluated in vivo in BALB/c mice injected with CT26CL25 cells. Both agents suppressed the growth of colon cancer cells in vitro and reduced tumor volume in syngeneic BALB/c mice. However, their mechanisms of action were different because GIT-27NO released larger amounts of nitrite than Saq-NO in cell cultures and its antitumor action depended on the intracellular NO release inside the cells. On the contrary, Saq-NO released barely detectable amounts of NO and its antitumor action was NO-independent. In fact, cotreatment with an NO-peroxynitrite scavenger revealed that GIT-27NO but not Saq-NO acts through peroxynitrite-mediated cell destruction. At the cellular level, GIT-27NO prevalently induced proapoptotic signals followed by caspase-dependent apoptosis. In contrast, Saq-NO blocked cell proliferation, changed the adhesive, migratory, and invasive properties of the cells, and decreased metastatic potential in vivo. In conclusion, differences in NO release and oxidative stress generation between GIT-27NO and Saq-NO resulted in different mechanisms that caused cell death.", publisher = "Amer Soc Pharmacology Experimental Therapeutics, Bethesda", journal = "Molecular Pharmacology", title = "Therapeutic Potential of Nitric Oxide-Modified Drugs in Colon Cancer Cells", pages = "710-700", number = "4", volume = "82", doi = "10.1124/mol.112.077842" }
Mojić, M., Mijatović, S., Maksimović-Ivanić, D., Miljković, D., Stošić-Grujičić, S., Stanković, M., Mangano, K., Travali, S., Donia, M., Fagone, P., Zocca, M., Al-Abed, Y., McCubrey, J. A.,& Nicoletti, F.. (2012). Therapeutic Potential of Nitric Oxide-Modified Drugs in Colon Cancer Cells. in Molecular Pharmacology Amer Soc Pharmacology Experimental Therapeutics, Bethesda., 82(4), 700-710. https://doi.org/10.1124/mol.112.077842
Mojić M, Mijatović S, Maksimović-Ivanić D, Miljković D, Stošić-Grujičić S, Stanković M, Mangano K, Travali S, Donia M, Fagone P, Zocca M, Al-Abed Y, McCubrey JA, Nicoletti F. Therapeutic Potential of Nitric Oxide-Modified Drugs in Colon Cancer Cells. in Molecular Pharmacology. 2012;82(4):700-710. doi:10.1124/mol.112.077842 .
Mojić, Marija, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Miljković, Djordje, Stošić-Grujičić, Stanislava, Stanković, Marija, Mangano, Katia, Travali, Salvatore, Donia, Marco, Fagone, Paolo, Zocca, Mai-Britt, Al-Abed, Yousef, McCubrey, James A., Nicoletti, Ferdinando, "Therapeutic Potential of Nitric Oxide-Modified Drugs in Colon Cancer Cells" in Molecular Pharmacology, 82, no. 4 (2012):700-710, https://doi.org/10.1124/mol.112.077842 . .