The presence of a knot strongly weakens the polymer that potentially breaks

We analyzed cell migration by a wound healing assay. We found that ODDHSL exposure inhibited the migration of both Panc-1 and Aspc-1 cells, while untreated cells were able to completely close the wound gap. Based on these results, we hypothesized that the genes involved in cell motility could be a target for O-DDHSL. It is possible that migration could be affected by O-DDHSL induced apoptosis but the concentration of the compound added was reduced to near IC50 values to minimize apoptosis. It was difficult to assess the effect of O-DDHSL on HPDE cells as the wound healing ability was found to be similar in untreated and cells treated with O-DDHSL. It is likely that the ability of normal pancreatic epithelial cells to close the wound gap is rather a slow process compared to carcinoma cells. To further gain MK-0683 insight into the inhibition of cell migration by O-DDHSL, we focused on three important genes which are essential for cell migration including Torin 1 cofilin IQGAP-1 and the small GTPase RhoC. Cofilin is an important regulator of actin cytoskeleton and IQGAP-1 localizes in the leading edge of migrating cells. RhoC is a small GTPase which is an important effector of tumor cell motility and is expressed in pancreatic tumors. Similarly, cofilin is also present in pancreatic carcinoma tissues and possibly promotes its progression. Upon treatment with O-DDHSL, the mRNA message of cofilin increased in HPDE and Panc-1 cells. The endogenous mRNA expression of RhoC increased in O-DDHSL treated Panc-1, Aspc1 and HPDE cells. In HPDE cells, upon O-DDHSL treatment a decrease in IQGAP-1 was noted but the change was only marginal in Panc-1 and Aspc-1 cells. Protein expression studies indicated that in O-DDHSL treated cells no drastic changes were observed in case of IQGAP-1or RhoC in tumor cells except for HPDE cells. Altogether, O-DDHSL differentially modulates the gene expression of cofilin, RhoC and IQGAP-1, all involved in cell migration. IQGAP-1 was reported to be targeted by O-DDHSL in Caco-2 epithelial cells affecting their migration.

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