PMID- 24861078
OWN - NLM
STAT- MEDLINE
DCOM- 20150330
LR  - 20220410
IS  - 1208-6002 (Electronic)
IS  - 0829-8211 (Linking)
VI  - 92
IP  - 3
DP  - 2014 Jun
TI  - Targeting angiogenic pathway for chemoprevention of experimental colon cancer 
      using C-phycocyanin as cyclooxygenase-2 inhibitor.
PG  - 206-18
LID - 10.1139/bcb-2014-0016 [doi]
AB  - An angiogenic pathway was studied that involved stromal tissue degradation with 
      matrix metalloproteinases (MMPs), vesicular endothelial growth factor-A (VEGF-A), 
      and hypoxia inducible factor-1alpha (HIF-1alpha) mediated growth regulation in a complex 
      interaction with chemokines, such as monocyte chemoattractant protein-1 (MCP-1) 
      and macrophage inflammatory protein-1beta (MIP-1beta). Gene and protein expression was 
      studied with real-time PCR, Western immunoblot, and immunofluorescence. 
      Morphological and histopathological analysis of tumor was done, as also the 
      activity of MMPs and HIF-1alpha by gelatin zymography and ELISA. Binding interactions 
      of proteins were studied by molecular docking. Piroxicam, a traditional NSAID and 
      C-phycocyanin, a biliprotein from Spirulina platensis, were utilized in the 
      chemoprevention of DMH-induced rat colon cancer. A significant number of tumors 
      was evident in DMH treated animals, while with piroxicam and C-phycocyanin, the 
      number and size of tumors/lesions were reduced. Colonic tissues showed severe 
      dysplasia, tubular adenoma, and adenocarcinoma from DMH, with invasive features 
      along with signet ring cell carcinoma. No occurrence of carcinoma was detected in 
      either of the drug treatments or in a combination regimen. An elevated VEGF-A, 
      MMP-2, and MMP-9 level was observed, which is required for metastasis and 
      invasion into surrounding tissues. Drugs induced chemoprevention by 
      down-regulating these proteins. Piroxicam docked in VEGF-A binding site of VEGF-A 
      receptors i.e., VEGFR1 and VEGFR2, while phycocyanobilin (a chromophore of 
      C-phycocyanin) docked with VEGFR1 alone. HIF-1alpha is up-regulated which is 
      associated with increased oxygen demand and angiogenesis. MCP-1 and MIP-1beta 
      expression was also found altered in DMH and regulated by the drugs. 
      Anti-angiogenic role of piroxicam and C-phycocyanin is well demonstrated.
FAU - Saini, Manpreet Kaur
AU  - Saini MK
AD  - Department of Biophysics, Panjab University, Chandigarh 160014, India.
FAU - Sanyal, Sankar Nath
AU  - Sanyal SN
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140424
PL  - Canada
TA  - Biochem Cell Biol
JT  - Biochemistry and cell biology = Biochimie et biologie cellulaire
JID - 8606068
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Cyclooxygenase 2 Inhibitors)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 11016-15-2 (Phycocyanin)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/chemistry/*pharmacology
MH  - Colonic Neoplasms/*drug therapy/pathology
MH  - Cyclooxygenase 2/*metabolism
MH  - Cyclooxygenase 2 Inhibitors/chemistry/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Male
MH  - Models, Molecular
MH  - Neoplasms, Experimental/*drug therapy/pathology
MH  - Neovascularization, Pathologic/*drug therapy/metabolism/pathology
MH  - Phycocyanin/chemistry/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Structure-Activity Relationship
MH  - Vascular Endothelial Growth Factor A/metabolism
OTO - NOTNLM
OT  - HIF-1alpha
OT  - MCP-1
OT  - MIP-1ss
OT  - MIP-1beta
OT  - MMP
OT  - MMPs
OT  - VEGF-A
EDAT- 2014/05/28 06:00
MHDA- 2015/03/31 06:00
CRDT- 2014/05/28 06:00
PHST- 2014/05/28 06:00 [entrez]
PHST- 2014/05/28 06:00 [pubmed]
PHST- 2015/03/31 06:00 [medline]
AID - 10.1139/bcb-2014-0016 [doi]
PST - ppublish
SO  - Biochem Cell Biol. 2014 Jun;92(3):206-18. doi: 10.1139/bcb-2014-0016. Epub 2014 
      Apr 24.