Anti-pancreatic cancer activity of Z-ajoene from garlic: An inhibitor of the Hedgehog/Gli/FoxM1 axis.

• Z-Ajoene modulates Hedgehog/Gli pathway by reducing Gli transcriptional activity. • Z-Ajoene inhibits expressions of Gli- and FoxM1-target proteins in PANC-1 cells. • Z-Ajoene inhibits growth of PANC-1 cells via cell cycle arrest at G2/M phase. Overexpression of glioma-associated oncogene (Gli), a transcription factor at the final step of Hedgehog (Hh) pathway, is involved in pancreatic cancer development. Therefore, inhibition of Gli can be a therapeutic strategy to treat pancreatic cancer. The objective of this study was to determine effects of Z-ajoene from garlic, on Gli-mediated transcription and proliferation of pancreatic cancer cells. We found that Z-ajoene could inhibit Gli transcriptional activity in Sonic Hedgehog (Shh) stimulated C3H10T1/2 mesenchymal stem cells. Z-Ajoene suppressed Gli transcriptional activity and Gli-target protein expressions in PANC-1 human pancreatic cancer cells. Z-Ajoene also reduced expression of FoxM1, one of Gli-target proteins, and subsequently down-regulated expressions of cell cycle-related proteins. Moreover, Z-ajoene reduced cell proliferation and increased G2/M phase of PANC-1 cells. These results suggest that Z-ajoene can repress pancreatic cancer cell proliferation by inhibiting Gli signaling. Thus, Z-ajoene might be a lead compound for the development of anti-pancreatic cancer agent. [ABSTRACT FROM AUTHOR]