Curcumin Regulates Colon Cancer by Inhibiting P-Glycoprotein in In-situ Cancerous Colon Perfusion Rat Model
|Prasad Neerati1*, Yakkanti A. Sudhakar2, Jagat R Kanwar3|
|1DMPK & Clinical Pharmacology Division, Department of Pharmacology, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, AP, 506009, India|
|2Cell signaling Laboratory, Bioscience Division, Center for Cancer and Metabolism, SRI International, Menlo PArk, CA 94025, USA|
|3Nanomedicine-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|
|Corresponding Author :||Prasad Neerati, Ph.D
Assistant Professor of Pharmacy
DMPK & Clinical Pharmacology Division
Department of Pharmacology
University College of Pharmaceutical Sciences
Kakatiya University, Warangal, AP, India
E-mail: [email protected]
|Received June 26, 2013; Accepted July 02, 2013; Published July 08, 2013|
|Citation: Neerati P, Sudhakar YA, Kanwar JR (2013) Curcumin Regulates Colon Cancer by Inhibiting P-Glycoprotein in In-situ Cancerous Colon Perfusion Rat Model. J Cancer Sci Ther 5:313-319. doi: 10.4172/1948-5956.1000221|
|Copyright: © 2013 Neerati P, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
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Study background: Studies on p-glycoprotein was carried out world vide with cell lines like Caco2, MDR1- LLC-PK1 and MDR1-MDCK in-vitro, but most of the results were failed to produce similar results in-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 colon in-situ perfusion 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.