A Study On Molecular Mechanism Of The Anti-tumor Effect Of Petasin On Neuroblastoma

Scanning effective anti-tumor compounds from natural products has been aresearch focus in tumor treatment, and also a hot area in current drug industryresearch. Petasin is one of the major active ingredients in the petasites. Recent datafrom our lab and other research groups showed the anti-tumor effects of petasin on avariety of cancer cells. SH-SY5Y cell line is subclone of SK-N-SH cell line andshows many similarities in malignancy. However, they show significant difference inIC50and apoptosis when treated with petasin, suggesting different molecularmechanisms involved in such phenomenon.In the present study, we compared the differential expression genes between thetest group (petasin treated) and control group(without petasin) both in SK-N-SH andSH-SY5Y cell using gene chips. Results showed that after8hours treatment withpetasin, there were15significant differential genes expressed in SK-N-SH cellgroups, in which10were up-regulated and5were down-regulated, and there were90significant differential genes expressed in SH-SY5Y cell groups, among which,48were up-regulated and42were down-regulated. The results of gene chip werevalidated by RT-qPCR. We then determined the temporal pattern of egr1, ctgf andgadd45a expression in either SK-N-SH cells or SH-SY5Y cells after petasintreatment. The results showed that egr1can be induced by petasin transiently andsignificantly both in SK-N-SH cell and SH-SY5Y cell. With the time prolongation,the expression of egr1was declined in SK-N-SH cell, while returned to normal levelsin SH-SY5Y cell. Exposure of cells to petasin8h caused down-regulation of ctgf inSK-N-SH and the inhibition maintained with the prolonging of time. On the otherhand, the expression of gadd45a was stable in SK-N-SH during all the periods withpetasin treatment. Conversely, petasin could up-regulate gadd45a after4h inSH-SY5Y.In conclusion, petasin induced a variety of genes expression changes both inSK-N-SH cell and SH-SY5Y cell, such as tumor suppressor genes, cyclin genes,signal conduction-related genes, transcription factor genes, cell metabolic regulation genes, cell death-related genes, etc. The proliferation inhibition and cell cycle arresteffects of petasin on SK-N-SH cell may be related to the regulation of egr1and/orctgf signaling pathway, while gadd45a may directly or indirectly be involved in theproliferation inhibition effect of petasin on SH-SY5Y cell.