Tomatidine inhibits cell invasion through the negative modulation of gelatinase and inactivation of p38 and ERK. (1st November 2019)

• Record Type: Journal Article
• Authors: Jeon, Sojeong; Kim, Moon-Moo
• Is Part Of: Chemico-biological interactions. Volume 313(2019)
• Publication Date: 2019-11-01
• Subjects: Tomatidine -- Gelatinase -- Metastasis -- AP-1 -- p38 -- ERK; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2019.108826
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Background: Despite of the most effective surgical removal of malignant tumors, metastasis makes cancer treatment difficult. The studies on natural compounds to inhibit this metastasis have been actively performed until now. However, the effect of tomatidine on metastasis remains unclear. Method: The effect of tomatidine on antioxidative activity was measured with DPPH radical assay and reducing power assay. After treatment with tomatidine, the viability of human fibrosarcoma cells (HT1080 cells) was evaluated with MTT assay. The effect of tomatidine on the inhibition of matrix metalloproteinase-2 (MMP-2) and MMP-9, gelatinases related to metastasis, was analyzed using gelatin zymography, western blot and immunofluorescence staining. Cell invasion assay was used to investigate anti-metastasis activity of tomatidine. Result: Tomatidine showed no DPPH radical scavenging effect and showed 8% of reduction power at 8 μM. Furthermore, tomatidine below 8 μM showed more than 80% of cell viability in MTT assay. The inhibition of tomatidine on MMP-2 activity and its protein expression levels were observed by gelatin zymography, western blot and immunofluorescence. It was observed that tomatidine inhibited not only p38 and ERK but also cell invasion. Conclusion: Above results suggest that tomatidine could use as a potential candidate for cancer prevention and metastasis through the inhibitory effect on gelatinase. Graphical abstract: Image 1 Highlights: Tomatidine inhibits MMP-2 activity. Tomatidine inhibits MMP-2 protein expression. Tomatidine inhibits p38 and ERK. Tomatidine inhibits cell invasion.