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VSP-17, a novel peroxisome proliferator-activated receptor γ (PPARγ) agonist, has been previously demonstrated to suppress the metastasis of triple-negative breast cancer (TNBC) by upregulating the expression levels of E-cadherin, which is a key marker of epithelial-mesenchymal transition (EMT). However, the mechanism of action of VSP-17, in particular whether it may be associated with the EMT process, remains unknown. The present study investigated the ability of VSP-17 to inhibit the invasiveness and migratory ability of TNBC cell lines (MDA-MB-231 and MDA-MB-453) performed in in vitro experiments. including cell migration assay, cell invasion assay, cell transfection, RT-qPCR, western blot (WB) analysis and immunofluorescence. The present study aimed to ascertain whether and how the PPARγ/AMP-activated protein kinase (AMPK) signaling pathway serves a role in the inhibitory effects of VSP-17 on cell migration and invasion. The results revealed that both treatment with compound C (an AMPK inhibitor) and transfection with small interfering RNA (si)AMPK notably diminished the inhibitory effect of VSP-17 treatment on the migration and invasion of MDA-MB-231 and MDA-MB-453 cells, indicating that VSP-17 may, at least partly, exert its effects via AMPK. Furthermore, both compound C and siAMPK markedly diminished the VSP-17-induced downregulation of vimentin expression levels and upregulation of E-cadherin expression levels, further indicating that the VSP-17-induced inhibition of the EMT process may be dependent on AMPK. The combination of GW9662 (a PPARγ antagonist) or siPPARγ diminished the inhibitory effect of VSP-17 treatment on the migration and invasion of the TNBC cells, indicating that PPARγ may serve an important role in the VSP-17-induced inhibition of the migration and invasion of TNBC cells. In addition, both GW9662 and siPPARγ significantly reversed the VSP-17-induced downregulation of vimentin expression levels and upregulation of E-cadherin expression levels, implying that the VSP-17-induced inhibition of the EMT process may be dependent on PPARγ. VSP-17 treatment also upregulated the expression levels of p-AMPK, which could be reversed by either GW9662 or siPPARγ, indicating that the VSP-17-induced activation of the AMPK signaling pathway was PPARγ-dependent. In conclusion, the findings of the present study indicated that VSP-17 treatment may inhibit the migration and invasion of TNBC cells by suppressing the EMT process via the PPARγ/AMPK signaling pathway.

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p-Hydroxybenzoic acid (p-HBA), which exists extensively in plants, is well known for its anti-inflammatory effects, but various adverse side effects have also been reported. Previous research has found that acid translated to its sodium salt improves the safety profile of compounds. Therefore, we hypothesized that p-HBA translated to sodium p-hydroxybenzoate would improve its safety profile. In the present study, we evaluated the toxicity of sodium p-hydroxybenzoate after 90 days of repeated oral toxicity experiments according to OECD guidelines in male and female Sprague–Dawley rats. Sodium p-hydroxybenzoate was administered orally to SD rats at doses of 0, 125, 250, and 500 mg/kg body weight (BW)/day for 90 days. All animals survived to the end of the study, and no sodium p-hydroxybenzoate treatment-associated mortality or clinical changes were observed during the study period. Sodium p-hydroxybenzoate did not promote any clinical signs of toxicologically relevant effects, including changes in body weight, food intake and urinalysis parameters, in male or female SD rats. Dose-related alterations in hematological parameters, organ weights and histopathological findings in hepatic tissue were examined in animals of both sexes in the 500 mg/kg BW/day group. Based on the study, the no-observed-adverse-effect level (NOAEL) for sodium p-hydroxybenzoate was determined to be 250 mg/kg BW/day in both male and female rats.