The effects of cannabinoids on P-glycoprotein transport and expression in multidrug resistant cells

Holland, ML; Panetta, JA; Hoskins, JM; Bebawy, M; Roufogalis, BD; Allen, JD; Arnold, JC

The effects of cannabinoids on P-glycoprotein transport and expression in multidrug resistant cells

Holland, ML Panetta, JA Hoskins, JM Bebawy, M

Roufogalis, BD Allen, JD Arnold, JC

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Publication Type:: Journal Article
Citation:: Biochemical Pharmacology, 2006, 71 (8), pp. 1146 - 1154
Issue Date:: 2006-04-14

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Field	Value	Language
dc.contributor.author	Holland, ML	en_US
dc.contributor.author	Panetta, JA	en_US
dc.contributor.author	Hoskins, JM	en_US
dc.contributor.author	Bebawy, M https://orcid.org/0000-0003-2606-921X	en_US
dc.contributor.author	Roufogalis, BD	en_US
dc.contributor.author	Allen, JD	en_US
dc.contributor.author	Arnold, JC	en_US
dc.date.available	2005-12-27	en_US
dc.date.issued	2006-04-14	en_US
dc.identifier.citation	Biochemical Pharmacology, 2006, 71 (8), pp. 1146 - 1154	en_US
dc.identifier.issn	0006-2952	en_US
dc.identifier.uri	http://hdl.handle.net/10453/16974
dc.description.abstract	Cannabis is the most widely used illicit drug in the world. Cannabinoids are used therapeutically by some patients as they have analgesic, anti-emetic and appetite stimulant properties which palliate adverse symptoms. Use of these agents in an oncology setting raises the question of whether they act to modulate the effectiveness of concurrently administered anti-cancer drugs. The transporter, P-glycoprotein (P-gp) confers multiple drug resistance (MDR) by effluxing a diverse array of anti-cancer agents. This study was undertaken to examine the effect of cannabinoids on P-gp. Unlike the known P-gp inhibitor, PSC833, short 1 h exposure to three plant-derived cannabinoids, cannabinol (CBN), cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) and the synthetic cannabinoid receptor agonist, WIN55, 212-2 (WIN) did not inhibit the efflux of the P-gp substrate Rhodamine 123 (Rh123) in either a drug-selected human T lymphoblastoid leukaemia cell line (CEM/VLB100) or in a mouse fibroblast MDR1 transfected cell line (77.1). However, in CEM/VLB 100 cells, prolonged 72 h exposure to the cannabinoids, THC and CBD, decreased P-gp expression to a similar extent as the flavonoid, curcumin (turmeric). This correlated with an increase in intracellular accumulation of Rh123 and enhanced sensitivity of the cells to the cytotoxic actions of the P-gp substrate, vinblastine. Taken together, these results provide preliminary evidence that cannabinoids do not exacerbate P-gp mediated MDR. Further, plant-derived cannabinoids are moderately effective in reversing MDR in CEM/VLB100 cells by decreasing P-gp expression. © 2006 Elsevier Inc. All rights reserved.	en_US
dc.relation.ispartof	Biochemical Pharmacology	en_US
dc.relation.isbasedon	10.1016/j.bcp.2005.12.033	en_US
dc.subject.classification	Pharmacology & Pharmacy	en_US
dc.subject.mesh	Cell Line, Tumor	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Cannabinoids	en_US
dc.subject.mesh	P-Glycoprotein	en_US
dc.subject.mesh	Antineoplastic Agents	en_US
dc.subject.mesh	Drug Resistance, Multiple	en_US
dc.subject.mesh	Cell Survival	en_US
dc.subject.mesh	Protein Transport	en_US
dc.subject.mesh	Dose-Response Relationship, Drug	en_US
dc.subject.mesh	Drug Resistance, Neoplasm	en_US
dc.subject.mesh	ATP Binding Cassette Transporter, Subfamily B, Member 1	en_US
dc.title	The effects of cannabinoids on P-glycoprotein transport and expression in multidrug resistant cells	en_US
dc.type	Journal Article
utslib.citation.volume	8	en_US
utslib.citation.volume	71	en_US
utslib.for	1115 Pharmacology and Pharmaceutical Sciences	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
dc.location.activity	WOS:000236498300005	en_US
dc.location.activity	WOS:000287570200016
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Graduate School of Health
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	closed_access
pubs.issue	8	en_US
pubs.publication-status	Published	en_US
pubs.volume	71	en_US

Abstract:

Cannabis is the most widely used illicit drug in the world. Cannabinoids are used therapeutically by some patients as they have analgesic, anti-emetic and appetite stimulant properties which palliate adverse symptoms. Use of these agents in an oncology setting raises the question of whether they act to modulate the effectiveness of concurrently administered anti-cancer drugs. The transporter, P-glycoprotein (P-gp) confers multiple drug resistance (MDR) by effluxing a diverse array of anti-cancer agents. This study was undertaken to examine the effect of cannabinoids on P-gp. Unlike the known P-gp inhibitor, PSC833, short 1 h exposure to three plant-derived cannabinoids, cannabinol (CBN), cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) and the synthetic cannabinoid receptor agonist, WIN55, 212-2 (WIN) did not inhibit the efflux of the P-gp substrate Rhodamine 123 (Rh123) in either a drug-selected human T lymphoblastoid leukaemia cell line (CEM/VLB100) or in a mouse fibroblast MDR1 transfected cell line (77.1). However, in CEM/VLB 100 cells, prolonged 72 h exposure to the cannabinoids, THC and CBD, decreased P-gp expression to a similar extent as the flavonoid, curcumin (turmeric). This correlated with an increase in intracellular accumulation of Rh123 and enhanced sensitivity of the cells to the cytotoxic actions of the P-gp substrate, vinblastine. Taken together, these results provide preliminary evidence that cannabinoids do not exacerbate P-gp mediated MDR. Further, plant-derived cannabinoids are moderately effective in reversing MDR in CEM/VLB100 cells by decreasing P-gp expression. © 2006 Elsevier Inc. All rights reserved.

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http://hdl.handle.net/10453/16974