Nitric oxide donors or nitrite counteract copper-[dithiocarbamate](2)-mediated tumor cell death and inducible nitric oxide synthase down-regulation: possible role of a nitrosyl-copper [dithiocarbamate](2) complex

Journal of Medicinal Chemistry
Maricela Viola RhenalsManuel Rieber

Abstract

In contrast to other metal-dithiocarbamate [DEDTC] complexes, the copper-DEDTC complex is highly cytotoxic, inducing oxidative stress, preferentially in tumor cells. Because nitric oxide (NO) forms adducts with Cu[DEDTC](2), we investigated whether NO donors like S-nitroso-N-acetyl penicillamine (SNAP) or sodium nitroprusside (SNP), and nitrite, a NO decomposition product, modulate Cu[DEDTC](2) cytotoxicity against human tumor cells. We show that apoptosis-associated PARP cleavage and inducible nitric oxide synthase (iNOS) down-regulation induced by nanomolar Cu[DEDTC](2), are counteracted by 50 muM SNAP, SNP, or CoCl(2), an inducer of hypoxia and NO signaling. Nitrite was stochiometrically effective in antagonizing Cu[DEDTC](2) cytotoxicity and inducing shifts in the absorption spectrum of the binary complex in the 280 and 450 nm regions. Subtoxic concentrations of Cu[DEDTC](2) became lethal when tumor cells were pretreated with c-PTIO, a membrane-impermeable scavenger for extracellular NO. Our results suggest that: (a) reactive oxygen species induced by Cu[DEDTC](2) are scavenged by nitrite released from NO, (b) the extent of lethality of Cu[DEDTC](2) is dependent on the reciprocal formation of an inactive ternary Cu[DEDTC](2...Continue Reading

References

Mar 31, 1993·Biochemical and Biophysical Research Communications·M P ShermanL J Ignarro
Jan 10, 1995·Archives of Biochemistry and Biophysics·M R GuntherM S Cohen
Jul 1, 1996·Analytical Biochemistry·J A CookD A Wink
Sep 15, 2001·Free Radical Biology & Medicine·F L MeyskensR I Gonzalez
Sep 26, 2001·Experimental Cell Research·C SoldaniA I Scovassi
Jun 24, 2003·Journal of Inorganic Biochemistry·Alicia DíazFelipe Brito
Jul 31, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Lei XiRakesh C Kukreja
Dec 24, 2004·Journal of Medicinal Chemistry·Dazhi CenPatrick J Farmer
Aug 7, 2007·Biochemical Pharmacology·Maricela Viola-RhenalsManuel Rieber
Jul 2, 2008·Laboratory Investigation; a Journal of Technical Methods and Pathology·Pichili V B ReddyMichael D Norenberg
Aug 30, 2008·The Journal of General Physiology·Bhupesh MehtaPreeti G Joshi
Jan 9, 2009·International Journal of Cancer. Journal International Du Cancer·Verena FetzShirley K Knauer
Apr 21, 2009·Ageing Research Reviews·Francesca MangialaschePatrizia Mecocci

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis