Screening of a FDA-Approved Compound Library Identifies Menadione in Regulating Colon Cancer Programmed Death via MAPK8 Cascades

Abstract Colorectal cancer (CRC) is a conventional gastrointestinal malignant tumor, ranking third among all type of tumors and the fifth in clinical mortality. Programed cell death including apoptosis, autophagy and necroptosis that can be distinguished by their morphological and physiological differences. Although various researches and strategies were developed for anti-cancer drugs, there still lack of the effective therapies trigger cell programmed death to eliminate malignant colon tumor cells. In this study, we explored novel agents for inducing the programmed cell death through drug repurposing. We generated a high-throughput screening of a FDA Approved Drug Library, and identified Menadione, a synthetic analogue of vitamin K, as a promising candidate in regulating colon tumor programmed death. To further investigate the underlying mechanisms of Menadione in tumor programmed death, the selected gene of PCR array were performed and the data analysis showed significantly up-regulated gene by Menadione were ATG7 and MAPK8. The Go enrichment analysis also certify that MAPK8 may be an important regulation gene for Menadione induced cell apoptosis and necrosis in colorectal cancer. MAPK8 participated in multiple signaling pathways in GO enrichment analysis and KEGG pathway enrichment analysis, further demonstrated the key regulatory role of MAPK8. Thus, we identified Menadione may be a potential compound for MAPK8-targeting cascade. Owing to their FDA-approved status, Menadione might be used rapidly in the clinical treatment of tumor therapy. We demonstrated and provided new insights into the anti-cancer drug strategies.