title: Curcumin Regulates Colon Cancer by Inhibiting P-Glycoprotein inIn-situCancerous Colon Perfusion Rat Model.
abstract: BACKGROUND
  Studies on p-glycoprotein was carried out world vide with cell lines like Caco2, MDR1-LLC-PK1 and MDR1-MDCKin-vitro, but most of the results were failed to produce similar resultsin-vivo.In the present study curcumin inhibitory action on p-glycoprotein increased permeability of irinotecan, so in the colon cancer it would be beneficial if curcumin used as add on therapy.
  
  
  METHODS
  Intra-rectal administered of N-Nitroso N-methyl urea (2 mg/Kg) induced colon cancer. Single pass whole length of colonin-situperfusion was carried out in rats with irinotecan to study the influence of p-glycoprotein modulators like verapamil and curcumin. The rats were divided in to 5 groups (n=6), Group I served as control perfused with 30 μg/ml of irinotecan, propronolol and phenol red. Group II was cancerous group, induced by N-methyl N-nitroso urea. Group III was perfused with irinotican in cancerous rats. Group IV, perfused with irinotican in presence of verapamil and group V was pre-treated with curcumin and then perfused with irinotican and was estimated by HPLC-UV to effective permeability coefficient.
  
  
  RESULTS
  Our qRT-PCR and Western blot results confirmed that about 15-fold decreases in the expression of p-glycoprotein (P-gp) in curcumin treated colon cancer cells. Irinotecan was increased to 0.00066 cm/s and about 11-fold increase in verapamil-coperfused group, where curcumin pre-treated group irinotecan was increases 0.00006 cm/s to 0.00042 cm/s that is about 7-fold increase p-glycoprotein inhibitory activity by verapamil and curcumin found to be significantly enhanced the cancerous colon permeability of irinotecan.
  
  
  CONCLUSIONS
  Any safe suitable p-glycoprotein inhibitors along with irinotecan will enhance the therapeutic benefit in the treatment of the colon cancer.
authors: DMPK & Clinical Pharmacology Division, Department of Pharmacology, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, AP, 506009, India.
authors: Prasad
authors: P
authors: Neerati
authors: Cell signaling Laboratory, Bioscience Division, Center for Cancer and Metabolism, SRI International, Menlo PArk, CA 94025, USA.
authors: Yakkanti A
authors: YA
authors: Sudhakar
authors: Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), School of Medicine (SoM), Molecular and Medical Research (MMR) Strategic Research Centre, Faculty of Health, Deakin University, Waurn Ponds, Geelong, Victoria 3217, Australia.
authors: Jagat R
authors: JR
authors: Kanwar
keywords: Curcumin; Effective permeability; In situ colon perfusion; RP- HPLC; p-glycoprotein