Mechanisms underlying dimethyl sulfoxide-induced cellular migration in human normal hepatic cells

Abstract

Numerous studies have reported that low-dose dimethyl sulfoxide (DMSO, <1.5%, v/v) can interfere with various cellular processes, such as cell proliferation, differentiation, apoptosis, and cycle. By contrast, minimal information is available about the effect of low-dose DMSO on cell migration. Here, we report the effect of DMSO (0.0005%−0.5%, v/v) on cellular migration in human normal hepatic L02 cells. We used the Cell Counting Kit-8 assay to measure cell viability, scratch wound healing assay to observe cellular migration, flow cytometry to analyze cell cycle and death pattern, reverse transcription quantitative polymerase chain reaction to evaluate mRNA expression, and Western blot to detect protein levels. After treatment with 0.0005% (v/v) DMSO, more cells entered S phase arrest, the MMP1/TIMP1 ratio increased, and HSP27 expression was elevated. After treatment with 0.1% (v/v) DMSO, more cells entered G0/G1 phase arrest, the MMP2/TIMP2 ratio increased, the p-p38 and p-Smad3 signaling pathways were activated, and neuropilin-1 expression was elevated. These results showed that cells migrate when their MMP1/TIMP1 and MMP2/TIMP2 ratios are imbalanced. Such migration is modulated by the p38/HSP27 signaling pathway and TGF-β/Smad3 dependent signaling pathway.