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Anti-proliferative and anti-angiogenic effects of CB2R agonist (JWH-133) in non-small lung cancer cells (A549) and human umbilical vein endothelial cells: an in vitro investigation
B. Vidinský, P. Gál, M. Pilátová, Z. Vidová, P. Solár, L. Varinská, L. Ivanová, J. Mojžiš
Jazyk angličtina Země Česko
Typ dokumentu práce podpořená grantem
NLK
Free Medical Journals
od 2000
Freely Accessible Science Journals
od 2000
ProQuest Central
od 2005-01-01
Health & Medicine (ProQuest)
od 2005-01-01
ROAD: Directory of Open Access Scholarly Resources
od 2000
- MeSH
- buněčné kultury MeSH
- časové faktory MeSH
- endoteliální buňky pupečníkové žíly (lidské) účinky léků MeSH
- fragmentace DNA MeSH
- hojení ran MeSH
- kanabinoidy farmakologie metabolismus MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory plic farmakoterapie MeSH
- nemalobuněčný karcinom plic farmakoterapie MeSH
- patologická angiogeneze MeSH
- pohyb buněk MeSH
- proliferace buněk MeSH
- receptor kanabinoidní CB2 agonisté metabolismus MeSH
- viabilita buněk MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Non-small cell lung cancer has one of the highest mortality rates among cancer-suffering patients. It is well known that the unwanted psychotropic effects of cannabinoids (CBs) are mediated via the CB1 receptor (R), and selective targeting of the CB2R would thus avoid side effects in cancer treatment. Therefore, the aim of our study was to evaluate the effect of selective CB2R agonist, JWH-133, on A549 cells (non-small lung cancer) and human umbilical vein endothelial cells (HUVECs). Cytotoxicity assay and DNA fragmentation assay were employed to evaluate the influence of JWH-133 (3-(1,1-dimethylbutyl)- 1-deoxy-Δ8-tetrahydrocannabinol) on investigated cancer cells. In addition, migration assay and gelatinase zymography were performed in HUVECs to asses JWH-133 anti-angiogenic activity. Our study showed that JWH-133 exerted cytotoxic effect only at the highest concentration used (10-4 mol/l), while inhibition of colony formation was also detected at the non-toxic concentrations (10-5–10-8 mol/l). JWH-133 was also found to be able to induce weak DNA fragmentation in A549 cells. Furthermore, JWH-133 at non-toxic concentrations inhibited some steps in the process of angiogenesis. It significantly inhibited endothelial cell migration after 17 h of incubation at concentrations of 10-4–10-6 mol/l. In addition, JWH-133 inhibited MMP-2 secretion as assessed by gelatinase zymography. The present study demonstrates the in vitro anti-proliferative and anti-angiogenic potential of CB2R agonist, JWH-133, in nonsmall lung cancer cells and HUVECs. Our results generate a rationale for further in vivo efficacy studies with this compound in preclinical cancer models.
Department of Pathological Anatomy University of Veterinary Medicine and Pharmacy Košice
Department of Pharmacology Pavol Jozef Šafárik University Košice
Department of Pharmacology Pavol Jozef Šafárik University Košice Slovak Republic
East Slovak Institute of Cardiovascular Diseases Department for Biomedical Research Košice
Institute of Biology and Ecology Pavol Jozef Šafárik University Košice
Institute of Histology and Embryology 1st Faculty of Medicine Charles University Prague
Literatura
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- $a Non-small cell lung cancer has one of the highest mortality rates among cancer-suffering patients. It is well known that the unwanted psychotropic effects of cannabinoids (CBs) are mediated via the CB1 receptor (R), and selective targeting of the CB2R would thus avoid side effects in cancer treatment. Therefore, the aim of our study was to evaluate the effect of selective CB2R agonist, JWH-133, on A549 cells (non-small lung cancer) and human umbilical vein endothelial cells (HUVECs). Cytotoxicity assay and DNA fragmentation assay were employed to evaluate the influence of JWH-133 (3-(1,1-dimethylbutyl)- 1-deoxy-Δ8-tetrahydrocannabinol) on investigated cancer cells. In addition, migration assay and gelatinase zymography were performed in HUVECs to asses JWH-133 anti-angiogenic activity. Our study showed that JWH-133 exerted cytotoxic effect only at the highest concentration used (10-4 mol/l), while inhibition of colony formation was also detected at the non-toxic concentrations (10-5–10-8 mol/l). JWH-133 was also found to be able to induce weak DNA fragmentation in A549 cells. Furthermore, JWH-133 at non-toxic concentrations inhibited some steps in the process of angiogenesis. It significantly inhibited endothelial cell migration after 17 h of incubation at concentrations of 10-4–10-6 mol/l. In addition, JWH-133 inhibited MMP-2 secretion as assessed by gelatinase zymography. The present study demonstrates the in vitro anti-proliferative and anti-angiogenic potential of CB2R agonist, JWH-133, in nonsmall lung cancer cells and HUVECs. Our results generate a rationale for further in vivo efficacy studies with this compound in preclinical cancer models.
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