Pathology & Oncology Research

, Volume 18, Issue 4, pp 857–866

Revisiting CB1 Receptor as Drug Target in Human Melanoma

Authors

    • 2nd Department of PathologySemmelweis University
  • Balázs Bánki
    • 2nd Department of PathologySemmelweis University
  • Ágnes Márk
    • National Institute of Oncology
  • Norbert Varga
    • National Institute of Oncology
  • József Tóvári
    • National Institute of Oncology
  • Andrea Ladányi
    • National Institute of Oncology
  • Erzsébet Rásó
    • 2nd Department of PathologySemmelweis University
  • József Tímár
    • 2nd Department of PathologySemmelweis University
Research

DOI: 10.1007/s12253-012-9515-y

Cite this article as:
Kenessey, I., Bánki, B., Márk, Á. et al. Pathol. Oncol. Res. (2012) 18: 857. doi:10.1007/s12253-012-9515-y

Abstract

Previous studies have indicated the antitumoral effect of human melanocytes, human melanoma cell lines expressing CB1 receptor (CB1), and of the peritumoral administration of endocannabinoids. In the present study, we systematically screened several human melanoma cell lines for the expression of CNR1 and demonstrated transcription of the authentic gene. The product of CNR1, the CB1 protein, was found localized to the cell membrane as well as to the cytoskeleton. Further, the studied human melanoma cell lines expressed functional CB1 since physiological and synthetic ligands, anandamide (AEA), Met-F-AEA, ACEA and AM251 showed a wide range of biological effects in vitro, for example anti-proliferative, proapoptotic and anti-migratory. More importantly, our studies revealed that systemic administration of a stable CB1 agonist, ACEA, into SCID mice specifically inhibited liver colonization of human melanoma cells. Since therapeutic options for melanoma patients are still very limited, the endocannabinoid-CB1 receptor system may offer a novel target.

Keywords

CB1 receptor Endocannabinoid Human malignant melanoma Metastasis

Abbreviations

2-AG

2-arachidonoylglycerol

A

Adenosine

ACEA

Arachidonyl-2-chloroethylamide

AEA

Anandamide

AKT

Protein kinase B

AM251

N-piperidinyl-iodophenyl-dichlorophenyl-methylpyrazole-carboxamide

BSA

Bovine serum albumin

C

Cytosine

Ca

Calcium

CB

Cannabinoid

CB1

Cannabinoid receptor 1

CB2

Cannabinoid receptor 2

CNR1

Gene of cannabinoid receptor 1

cDNA

Complementary deoxyribonucleic acid

DEPC

Diethylpyrocarbonate

DMSO

Dimethyl sulfoxide

DNA

Deoxyribonucleic acid

COX

Cyclooxygenase

EDTA

Ethylenediaminetetraacetic acid

FAAH

Fatty acid amide hydrolase

FCS

Fetal calf serum

FITC

Fluorescein isothiocyanate

G

Guanine

GPCR

G protein-coupled receptor

IC50

Half maximal inhibitory concentration

IFN

Interferon

IL

Interleukin

LOX

Lipooxygenase

MAGL

Monoacylglycerol lipase

MAPK

Mitogen-activated protein kinase

Met-F-AEA

2-methyl-2-fluoro-anandamide

mTOR

Mammalian target of rapamycin

MTT

Thiazolyl blue tetrazolium bromide

P

Probability

PBS

Phosphate-buffered saline

PCR

Polymerase chain reaction

PI

Propidium iodide

PI3K

Phosphatidylinositol-3 kinase

RAF

RAF oncogene

RAS

RAS oncogene

Rb

Retinoblastoma

RNA

Ribonucleic acid

SCID

Severe combined immunodeficiency

T

Thymine

Copyright information

© Arányi Lajos Foundation 2012