Kim, Bo Ram Kim, Dae Yeong Tran, Na Ly Kim, Bu Gyeom Lee, Sun Il Kang, Sang Hee Min, Byung Yook Hur, Wooyoung Oh, Sang Cheul 2024-05-30T08:30:13Z 2024-05-30T08:30:13Z 2024-05-30 2024-06 1019-6439 https://pubs.kist.re.kr/handle/201004/149946 Daunorubicin, also known as daunomycin, is a DNA-targeting anticancer drug that is used as chemotherapy, mainly for patients with leukemia. It has also been shown to have anticancer effects in monotherapy or combination therapy in solid tumors, but at present it has not been adequately studied in colorectal cancer (CRC). In the present study, from a screening using an FDA-approved drug library, it was found that daunorubicin suppresses GLI-dependent luciferase reporter activity. Daunorubicin also increased p53 levels, which contributed to both GLI1 suppression and apoptosis. The current detailed investigation showed that daunorubicin promoted the beta-TrCP-mediated ubiquitination and proteasomal degradation of GLI1. Moreover, a competition experiment using BODIPY-cyclopamine, a well-known Smo inhibitor, suggested that daunorubicin does not bind to Smo in HCT116 cells. Administration of daunorubicin (2 mg/kg, ip, qod, 15 days) into HCT116 xenograft mice profoundly suppressed tumor progress and the GLI1 level in tumor tissues. Taken together, the present results revealed that daunorubicin suppresses canonical Hedgehog pathways in CRC. Ultimately, the present study discloses a new mechanism of daunorubicin's anticancer effect and might provide a rationale for expanding the clinical application of daunorubicin. English Demetrios A. Spandidos Ed. & Pub. Daunorubicin induces GLI1-dependent apoptosis in colorectal cancer cell lines Article 10.3892/ijo.2024.5654 1 International Journal of Oncology, v.64, no.6 International Journal of Oncology 64 6 Y scie scopus 001224308500001 2-s2.0-85193223079 Oncology Oncology Article HEDGEHOG EXPRESSION GLI1 PHOSPHORYLATION TRANSCRIPTION INHIBITION ACTIVATION PATHWAY SMO daunorubicin hedgehog signaling colorectal cancer GLI1 p53