C-Phycocyanin inhibits MDR1 through reactive oxygen species and cyclooxygenase-2 mediated pathways in human hepatocellular carcinoma cell line.
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.
Nishanth
Reddy P
RP
School of Life Sciences, University of Hyderabad, Hyderabad-500046, India.
Ramakrishna
B S
BS
Jyotsna
Radhika G
RG
Roy
Karnati R
KR
Reddy
Gorla V
GV
Reddy
Pratap K
PK
Reddanna
Pallu
P
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000903:Antibiotics, Antineoplastic / Q000378:metabolism / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects*; D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D010798:Phycocyanin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D010798:Phycocyanin; D004317:Doxorubicin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019255:NADPH Oxidases; D015232:Dinoprostone