Integrated transcriptomic and proteomic analysis reveals the mechanistic role of OST in cutaneous squamous cell carcinoma

Osthole (OST) is a natural component of the traditional Chinese medicinal herb, Cnidium monnieri, that exhibits antipruritic properties and may exert effects on dermatitis. Numerous previous studies have focused on the effects of OST in tumors; however, the potential impact on cutaneous squamous cell carcinoma (CSCC) remains to be fully elucidated. Thus, the present study aimed to evaluate CSCC cell proliferation following treatment with OST, and further analyzed the underlying mechanisms using multi-omics analyses. Due to their cancerous characteristics, both A431 and SCL-1 cells are used in drug screening and testing for CSCC, particularly for therapies targeting growth pathways and markers associated with SCC. Results of the flow cytometry analysis demonstrated that OST impacted the CSCC cell cycle, causing arrest in the G2 phase. Notably, OST exerted a slight growth-promoting effect on healthy skin HaCaT cells. In addition, our omics results revealed that there were 1,720 differentially expressed genes and 227 differentially expressed proteins in the OST-treated group. Transcriptomics combined with proteomics analyses revealed that 5 of the top 20 screened pathways were associated with the cell cycle, and ATR, CENPJ, and RAD54B were highlighted as specific targets for OST-mediated regulation. Collectively, these results suggested that OST has a potential inhibition on human CSCC cells, and ATR, CENPJ, and RAD54B may be the key factors regulated by OST in A431's cell cycle progression inhibition.