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Daunorubicin induces GLI1‑dependent apoptosis in colorectal cancer cell lines

  • Authors:
    • Bo Ram Kim
    • Dae Yeong Kim
    • Na Ly Tran
    • Bu Gyeom Kim
    • Sun Il Lee
    • Sang Hee Kang
    • Byung Yook Min
    • Wooyoung Hur
    • Sang Cheul Oh
  • View Affiliations / Copyright

    Affiliations: Division of Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University Guro Hospital, Seoul 08308, Republic of Korea, Division of Bio‑Medical Science & Technology, KIST School, University of Science and Technology (UST), Seoul 02792, Republic of Korea, Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308, Republic of Korea, Medicinal Materials Research Center, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea
    Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 66
    |
    Published online on: May 13, 2024
       https://doi.org/10.3892/ijo.2024.5654
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Abstract

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 β‑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.
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Copy and paste a formatted citation
Spandidos Publications style
Kim BR, Kim DY, Tran NL, Kim BG, Lee SI, Kang SH, Min BY, Hur W and Oh SC: Daunorubicin induces GLI1‑dependent apoptosis in colorectal cancer cell lines. Int J Oncol 64: 66, 2024.
APA
Kim, B.R., Kim, D.Y., Tran, N.L., Kim, B.G., Lee, S.I., Kang, S.H. ... Oh, S.C. (2024). Daunorubicin induces GLI1‑dependent apoptosis in colorectal cancer cell lines. International Journal of Oncology, 64, 66. https://doi.org/10.3892/ijo.2024.5654
MLA
Kim, B. R., Kim, D. Y., Tran, N. L., Kim, B. G., Lee, S. I., Kang, S. H., Min, B. Y., Hur, W., Oh, S. C."Daunorubicin induces GLI1‑dependent apoptosis in colorectal cancer cell lines". International Journal of Oncology 64.6 (2024): 66.
Chicago
Kim, B. R., Kim, D. Y., Tran, N. L., Kim, B. G., Lee, S. I., Kang, S. H., Min, B. Y., Hur, W., Oh, S. C."Daunorubicin induces GLI1‑dependent apoptosis in colorectal cancer cell lines". International Journal of Oncology 64, no. 6 (2024): 66. https://doi.org/10.3892/ijo.2024.5654
Copy and paste a formatted citation
x
Spandidos Publications style
Kim BR, Kim DY, Tran NL, Kim BG, Lee SI, Kang SH, Min BY, Hur W and Oh SC: Daunorubicin induces GLI1‑dependent apoptosis in colorectal cancer cell lines. Int J Oncol 64: 66, 2024.
APA
Kim, B.R., Kim, D.Y., Tran, N.L., Kim, B.G., Lee, S.I., Kang, S.H. ... Oh, S.C. (2024). Daunorubicin induces GLI1‑dependent apoptosis in colorectal cancer cell lines. International Journal of Oncology, 64, 66. https://doi.org/10.3892/ijo.2024.5654
MLA
Kim, B. R., Kim, D. Y., Tran, N. L., Kim, B. G., Lee, S. I., Kang, S. H., Min, B. Y., Hur, W., Oh, S. C."Daunorubicin induces GLI1‑dependent apoptosis in colorectal cancer cell lines". International Journal of Oncology 64.6 (2024): 66.
Chicago
Kim, B. R., Kim, D. Y., Tran, N. L., Kim, B. G., Lee, S. I., Kang, S. H., Min, B. Y., Hur, W., Oh, S. C."Daunorubicin induces GLI1‑dependent apoptosis in colorectal cancer cell lines". International Journal of Oncology 64, no. 6 (2024): 66. https://doi.org/10.3892/ijo.2024.5654
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