Prevention of supercritical carbon dioxide fluid extract from Chrysanthemum indicum Linnén on cutaneous squamous cell carcinomas progression following UV irradiation in mice

Abstract

Chrysanthemum indicum Linnén ( C. indicum ), a medicinal and food herb with various bioactive components, may be of beneficial use in cosmetics and the treatment of skin-related diseases. However, to date, few studies have been reported on its potential preventive and therapeutic effects on skin cancer. Therefore, the present study aimed to investigate the effect and potential mechanism of action of supercritical carbon dioxide extract from C. indicum (CI SCFE ) on UV-induced skin cancer in a mouse model. Kunming mice were allocated randomly to five treatment groups: Sham, model, low concentration CI SCFE , high concentration CI SCFE and positive control nicotinamide groups. The dorsal skin of mice was irradiated with UV light for 31 weeks. Histopathological changes, ELISA assays, immunohistochemical analysis and western blotting were performed to investigate the potential therapeutic effects of CI SCFE . The results showed that CI SCFE alleviated skin oxidative and inflammatory damage in a UV-induced mouse model of skin cancer. Moreover, CI SCFE suppressed abnormal activation of proto-oncogene c-Myc and the overexpression of Ki-67 and VEGF, and increased expression of the anti-oncogene PTEN, thereby reducing abnormal proliferation of the epidermis and blood vessels. Additionally, CI SCFE increased the protein expression levels of NAD-dependent protein deacetylase sirtuin-1 (SIRT1), Kelch-like ECH associated protein 1 (Keap1) and inhibited the expression of nuclear factor 2 erythroid 2-related factor 2 (Nrf2), phosphorylated (p)-p62 (Ser 349), p-p65 and acetyl-p65 proteins in a UV-induced skin cancer mouse model. In summary, CI SCFE exhibited potent anti-skin cancer activity, which may be attributed its potential effects on the p62/Keap1-Nrf2 and SIRT1/NF-κB pathways.