Visit our Expo - Redox and Inflammation signaling 2012

Session X : Cell death in cancer Poster X, 49
Sensitivity of human glioma cells to pro-apoptotic cannabinoid treatment is due to
specific expression of cannabinoid receptors
Liliana Konarska 1, Aleksandra Ellert-Miklaszewska 1, Bozena Kaminska 2, Wieslawa
A. Grajkowska 3, Konrad Gabrusiewicz 2, Malgorzata Danilkiewicz 2
1Dept. of Biochemistry and Clinical Chemistry, Medical University, Banacha 1 str., 02-
091 Warsaw, Poland, Email: konarska@nencki.gov.pl 2Lab. of Transcription
Regulation, Nencki Institute, Pasteura 3 str., 02-093 Warsaw, Poland, 3Dept. of
Pathology, Children’s Memorial Health Institute, Dzieci Polskich 20 str., 04-730
Warsaw, Poland
Cannabinoids, originally derived from Cannabis sativa, have been recently extensively
studied as potential antitumoral agents. In the current study we examined whether synthetic
cannabinoids with different receptor specificity are able to induce apoptosis in human glioma
cells and whether selective CB2 receptor activation is sufficient to effectively kill tumor cells.
Human glioma cell lines derived from highly malignant brain tumors, including T98G,
U373MG, U87MG and LN229 cells as well as 3 primary human glioma cell lines T3, T10
and T1Y1 were exposed to WIN55,212-2 (non-selective CB1/CB2 agonist) and JWH133
(CB2-selective agonist). The expression of CB1 and CB2 cannabinoid receptors was
investigated by RT-PCR and immunocytochemistry. WIN-55,212-2 decreased cell viability in
all examined cell lines and induced severe changes in cell morphology. Susceptibility of the
cells to JWH133 treatment correlated with the CB2 cannabinoid receptor expression. Both
cannabinoids, once effective, triggered a decrease of mitochondrial membrane potential,
cleavage of caspase-9 and effector caspases. Using immunohistochemistry we evaluated the
CB2 receptor expression in paraffin sections from various histopathological types of human
gliomas. Most of the analyzed tumors expressed significant levels of CB2 receptor. The
extent of CB2 expression in the tumour specimens was related to tumour malignancy, which
was in line with our RT-PCR and immunocytochemistry studies. We conclude that
cannabinoids are efficient inhibitors of human glioma cells growth, once the cells express
specific type of cannabinoid receptor. Due to the presence of the CB1 receptors on normal
cells, the use of a selective CB2 receptor agonist, such as JWH133, seems to be a better
choice for in vivo studies and in terms of potential therapeutic approaches. Supported by the
grant No. 06/2002 from the Polish Pharmacy and Medicine Development Foundation by
Polpharma S.A.
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