C-Phycocyanin inhibits MDR1 through reactive oxygen species and cyclooxygenase-2 mediated pathways in human hepatocellular carcinoma cell line

Reddy P Nishanth; B S Ramakrishna; Radhika G Jyotsna; Karnati R Roy; Gorla V Reddy; Pratap K Reddy; Pallu Reddanna

doi:10.1016/j.ejphar.2010.09.011

C-Phycocyanin inhibits MDR1 through reactive oxygen species and cyclooxygenase-2 mediated pathways in human hepatocellular carcinoma cell line

Eur J Pharmacol. 2010 Dec 15;649(1-3):74-83. doi: 10.1016/j.ejphar.2010.09.011. Epub 2010 Sep 19.

Authors

Reddy P Nishanth¹, B S Ramakrishna, Radhika G Jyotsna, Karnati R Roy, Gorla V Reddy, Pratap K Reddy, Pallu Reddanna

Affiliation

¹ School of Life Sciences, University of Hyderabad, Hyderabad-500046, India.

PMID: 20858479
DOI: 10.1016/j.ejphar.2010.09.011

Abstract

The effects of C-Phycocyanin (C-PC), a biliprotein from Spirulina platensis on the regulation of multidrug resistance-1 (MDR1), a poly glycoprotein in human hepatocarcinoma cell line, HepG2 were reported. The results revealed that a significant down regulation of MDR1 expression in C-PC treated HepG2 cells was through reactive oxygen species and cyclooxygenase-2 (COX-2) mediated pathways. C-PC in a concentration dependent manner increased the accumulation of doxorubicin in HepG2 cells and enhanced sensitivity of the cells to doxorubicin by 5 folds. The induction of MDR1 expression by PGE₂ and its down regulation by C-PC and DPI (Diphenylene iodonium, NADPH oxidase inhibitor) or by COX-2 knockdown suggest that the enhanced sensitivity of HepG2 cells to doxorubicin by C-PC is mediated by the down regulation of MDR1 expression. Further studies reveal the involvement of NF-κB and AP-1 in the C-PC induced down regulation of MDR1. Also the inactivation of the signal transduction pathways involving Akt, ERK, JNK and p38 by C-PC was observed. The present study thus demonstrates the efficacy of C-PC in overcoming the MDR1 mediated drug resistance in HepG2 cells by the down regulation of reactive oxygen species and COX-2 pathways via the involvement of NF-κB and AP-1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
Antibiotics, Antineoplastic / metabolism
Antibiotics, Antineoplastic / pharmacology
Antineoplastic Agents, Phytogenic / pharmacology*
Carcinoma, Hepatocellular / drug therapy*
Carcinoma, Hepatocellular / metabolism
Cell Proliferation / drug effects
Cyclooxygenase 2 / genetics
Cyclooxygenase 2 / metabolism*
Dinoprostone / metabolism
Dinoprostone / pharmacology
Down-Regulation / drug effects*
Doxorubicin / metabolism
Doxorubicin / pharmacology
Drug Synergism
Enzyme Inhibitors / pharmacology
Hep G2 Cells
Humans
Liver Neoplasms / drug therapy
Liver Neoplasms / metabolism
NADPH Oxidases / antagonists & inhibitors
Phycocyanin / pharmacology*
RNA, Messenger / metabolism
RNA, Small Interfering
Reactive Oxygen Species / metabolism*
Signal Transduction / drug effects
Up-Regulation / drug effects

Substances

ABCB1 protein, human
ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily B, Member 1
Antibiotics, Antineoplastic
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
RNA, Messenger
RNA, Small Interfering
Reactive Oxygen Species
Phycocyanin
Doxorubicin
Cyclooxygenase 2
PTGS2 protein, human
NADPH Oxidases
Dinoprostone