Piroxicam and C-phycocyanin Mediated Apoptosis in 1,2-dimethylhydrazine Dihydrochloride Induced Colon Carcinogenesis: Exploring the Mitochondrial Pathway

Nutr Cancer. 2012 Apr;64(3):409-18. doi: 10.1080/01635581.2012.655402. Epub 2012 Feb 27.

Abstract

Apoptosis is a synchronized procedure of cell death that is regulated by caspases and proapoptotic proteins. During apoptosis, translocation of cytochrome c, an electron carrier, from mitochondria into the cytosol is regulated by Bcl-2 family members. Cytochrome c in association with an apoptotic protease activating factor (Apaf), a proapoptotic protein essential for cell differentiation and procaspase-9 form the apoptosome complex, which consecutively activates effector caspase, caspase-3, and coordinate the implementation of apoptosis. In the current study, an attempt has been made to gain insight into piroxicam, a traditional nonsteroidal antiinflammatory drug and c-phycocyanin, a biliprotein from Spirulina platensis (cyanobacterium) mediated apoptosis in DMH-induced colon cancer. Male Sprague-Dawley rats were segregated into 5 groups: control, DMH, DMH + piroxicam, DMH + c-phycocyanin, and DMH + piroxicam + c-phycocyanin. Results illustrated that piroxicam and c-phycocyanin treatments stimulate cytochrome c release by downregulating the Bcl-2 (an antiapoptotic protein) expression significantly, while promoting the level of Bax (a proapoptotic protein), thereby activating caspases (caspases-9 and -3) and Apaf-1. The outcomes of the present study clearly signify that piroxicam and c-phycocyanin may mediate mitochondrial-dependent apoptosis in DMH-induced colon cancer. Moreover, apoptosis induction was more apparent in the combination regimen of piroxicam and c-phycocyanin than the individual drugs alone.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 1,2-Dimethylhydrazine / toxicity*
  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Apoptosis / drug effects*
  • Apoptotic Protease-Activating Factor 1 / genetics
  • Apoptotic Protease-Activating Factor 1 / metabolism
  • Carcinogens / toxicity
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Caspase 9 / genetics
  • Caspase 9 / metabolism
  • Colonic Neoplasms / chemically induced
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / pathology*
  • Cyclooxygenase 1 / genetics
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Cytochromes c / metabolism
  • Down-Regulation
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mitochondria / metabolism*
  • Phycocyanin / pharmacology*
  • Piroxicam / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Spirulina
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Apaf1 protein, rat
  • Apoptotic Protease-Activating Factor 1
  • Carcinogens
  • Membrane Proteins
  • bcl-2-Associated X Protein
  • Phycocyanin
  • Piroxicam
  • Cytochromes c
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Ptgs1 protein, rat
  • Ptgs2 protein, rat
  • Casp3 protein, rat
  • Casp9 protein, rat
  • Caspase 3
  • Caspase 9
  • 1,2-Dimethylhydrazine