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Screening of an FDA-Approved Drug Library: Menadione Induces Multiple Forms of Programmed Cell Death in Colorectal Cancer Cells via MAPK8 Cascades

Published:31 July 2025 DOI: 10.3390/ph18081145 PMID: 40872536
Liyuan Cao,?Weiwei Song,?Jinli Sun,?Yang Ge,?Wei Mu,?Lei Li

Abstract

Background: Colorectal cancer (CRC) is a prevalent gastrointestinal malignancy, ranking third in incidence and second in cancer-related mortality. Despite therapeutic advances, challenges such as chemotherapy toxicity and drug resistance persist. Thus, there is an urgent need for novel CRC treatments. However, developing new drugs is time-consuming and resource-intensive. As a more efficient approach, drug repurposing offers a promising alternative for discovering new therapies. Methods: In this study, we screened 1068 small molecular compounds from an FDA-approved drug library in CRC cells. Menadione was selected for further study based on its activity profile. Mechanistic analysis included a cell death pathway PCR array, differential gene expression, enrichment, and network analysis. Gene expressions were validated by RT-qPCR. Results: We identified menadione as a potent anti-tumor drug. Menadione induced three programmed cell death (PCD) signaling pathways: necroptosis, apoptosis, and autophagy. Furthermore, we found that the anti-tumor effect induced by menadione in CRC cells was mediated through a key gene: MAPK8. Conclusions: By employing methods of cell biology, molecular biology, and bioinformatics, we conclude that menadione can induce multiple forms of PCD in CRC cells by activating MAPK8, providing a foundation for repurposing the "new use" of the "old drug" menadione in CRC treatment.

Substances (12)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Z-VAD-FMK 187389-52-2 C22H30FN3O7 311 suppliers $38.00-$5672.00
Z-VAD-FMK 187389-52-2 C22H30FN3O7 311 suppliers $38.00-$5672.00
Z-VAD-FMK 187389-52-2 C22H30FN3O7 311 suppliers $38.00-$5672.00
Z-VAD-FMK 187389-52-2 C22H30FN3O7 311 suppliers $38.00-$5672.00
Necrostatin-1 4311-88-0 C13H13N3OS 258 suppliers $12.00-$2008.00
Necrostatin-1 4311-88-0 C13H13N3OS 258 suppliers $12.00-$2008.00
Necrostatin-1 4311-88-0 C13H13N3OS 258 suppliers $12.00-$2008.00
Necrostatin-1 4311-88-0 C13H13N3OS 258 suppliers $12.00-$2008.00
Birinapant 1260251-31-7 C42H56F2N8O6 163 suppliers $44.00-$4247.00
Birinapant 1260251-31-7 C42H56F2N8O6 163 suppliers $44.00-$4247.00

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