Abstract
Objective To observe the therapeutic effect of Carvacrol on oral squamous cell carcinoma (OSCC) and dissect underlying molecular mechanisms. Methods Keap1/Nrf2, NALP3, Vimentin, and E-cadherin expression was detected in OSCC and normal oral mucosa (NOM) tissues using immunofluorescence or western blot. When treated with Carvacrol or tert-butylhydroquinone (TBHQ) that activates Nrf2, the expression of Keap1/Nrf2/HO-1, epithelial-mesenchymal transition- (EMT-) related proteins, and NALP3 was examined in OSCC cells. Nrf2 was silenced by treatment with sh-Nrf2 or ML385. After silencing Nrf2 or Carvacrol treatment, cell proliferation and migration were assessed by clone formation and scratch and transwell tests in OSCC cells. Moreover, the expression of Keap1/Nrf2/HO-1, EMT-related proteins, and NALP3 was detected. Results Keap1/Nrf2, NALP3, Vimentin, and E-cadherin proteins were all significantly upregulated in OSCC than NOM tissues. Carvacrol significantly suppressed Keap1/Nrf2/HO-1 activation. Carvacrol or silencing Nrf2 markedly inhibited the expression of Keap1/Nrf2/HO-1, EMT-related proteins, and NALP3 inflammasome in OSCC cells. Furthermore, clone formation and migration capacities were suppressed following treatment with Carvacrol or Nrf2 depletion. The opposite results were found when there is overexpression of Nrf2. However, Carvacrol distinctly improved the cancer-promoting effect induced by Nrf2 overexpression. Conclusion Our findings suggested that Carvacrol ameliorated inflammation, proliferation, and migration for OSCC, which was related to inhibition of the Nrf2/Keap1 pathway.
Highlights
Oral squamous cell carcinoma (OSCC) is a heterogeneous cancer caused by the lining of the oral mucosa, which occupies 90% of all oral cancer cases globally [1]
The immunofluorescence showed that Nuclear factor erythroid 2-related factor (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) expression was upregulated in OSCC tissues compared to normal oral mucosa (NOM) tissues (Figures 1(a) and 1(b))
Western blot results confirmed the higher expression of Keap1 (Figures 1(c) and 1(d)), Nrf2 (Figures 1(c) and 1(e)), and NALP3 (Figures 1(c) and 1(f)) in OSCC specimens in comparison to NOM specimens
Summary
Oral squamous cell carcinoma (OSCC) is a heterogeneous cancer caused by the lining of the oral mucosa, which occupies 90% of all oral cancer cases globally [1]. Even though surgery combined with radiotherapy or chemotherapy has made great progress, OSCC patients exhibit the 5year survival rate of
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