Details

Autor(en) / Beteiligte

• Ramer, Robert
• Rohde, Anja
• Merkord, Jutta
• Rohde, Helga
• Hinz, Burkhard

Titel

Decrease of Plasminogen Activator Inhibitor-1 May Contribute to the Anti-Invasive Action of Cannabidiol on Human Lung Cancer Cells

Ist Teil von

• Pharmaceutical research, 2010-10, Vol.27 (10), p.2162-2174

Ort / Verlag

Boston: Boston : Springer US

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• Purpose Using human lung cancer cells, we evaluated the involvement of plasminogen activator inhibitor-1 (PAI-1) in the anti-invasive action of cannabidiol, a non-psychoactive cannabinoid. Methods Invasion was quantified by a modified Boyden chamber assay. PAI-1 protein in cell culture media and PAI-1 mRNA were determined by immunoblotting and RT-PCR, respectively. Results Cannabidiol caused a profound inhibition of A549 cell invasion, accompanied by a decreased expression and secretion of PAI-1. Cannabidiol's effects on PAI-1 secretion and invasion were suppressed by antagonists to CB₁ and CB₂ receptors as well as to transient receptor potential vanilloid 1. Recombinant human PAI-1 and PAI-1 siRNA led to a concentration-dependent up- and down-regulation of invasiveness, respectively, suggesting a crucial role of PAI-1 in A549 invasiveness. Evidence for a causal link between cannabidiol's effects on PAI-1 and invasion was provided by experiments showing a reversal of its anti-invasive action by addition of recombinant PAI-1 at non-proinvasive concentrations. Key data were confirmed in two other human lung cancer cell lines (H460, H358). In vivo, a significant downregulation of PAI-1 protein by cannabidiol was demonstrated in A549 xenografts. Conclusion Our data provide evidence for a hitherto unknown mechanism underlying the anti-invasive action of cannabidiol on human lung cancer cells.