Mahmoud Ahmed

Postdoc - Cancer Genomics

Regulation of Cell Cycle Progression through RB Phosphorylation by Nilotinib and AT-9283 in Human Melanoma A375P Cells


Journal article


Trang Minh Pham, Mahmoud Ahmed, Trang Huyen Lai, Md Entaz Bahar, Jin Seok Hwang, Rizi Firman Maulidi, Quang Nhat Ngo, Deok Ryong Kim
International Journal of Molecular Sciences, vol. 25, 2024


Cite

Cite

APA   Click to copy
Pham, T. M., Ahmed, M., Lai, T. H., Bahar, M. E., Hwang, J. S., Maulidi, R. F., … Kim, D. R. (2024). Regulation of Cell Cycle Progression through RB Phosphorylation by Nilotinib and AT-9283 in Human Melanoma A375P Cells. International Journal of Molecular Sciences, 25. https://doi.org/10.3390/ijms25052956


Chicago/Turabian   Click to copy
Pham, Trang Minh, Mahmoud Ahmed, Trang Huyen Lai, Md Entaz Bahar, Jin Seok Hwang, Rizi Firman Maulidi, Quang Nhat Ngo, and Deok Ryong Kim. “Regulation of Cell Cycle Progression through RB Phosphorylation by Nilotinib and AT-9283 in Human Melanoma A375P Cells.” International Journal of Molecular Sciences 25 (2024).


MLA   Click to copy
Pham, Trang Minh, et al. “Regulation of Cell Cycle Progression through RB Phosphorylation by Nilotinib and AT-9283 in Human Melanoma A375P Cells.” International Journal of Molecular Sciences, vol. 25, 2024, doi:10.3390/ijms25052956.


BibTeX   Click to copy

@article{pham2024a,
  title = {Regulation of Cell Cycle Progression through RB Phosphorylation by Nilotinib and AT-9283 in Human Melanoma A375P Cells},
  year = {2024},
  journal = {International Journal of Molecular Sciences},
  volume = {25},
  doi = {10.3390/ijms25052956},
  author = {Pham, Trang Minh and Ahmed, Mahmoud and Lai, Trang Huyen and Bahar, Md Entaz and Hwang, Jin Seok and Maulidi, Rizi Firman and Ngo, Quang Nhat and Kim, Deok Ryong}
}

Abstract

BCR-ABL tyrosine kinase inhibitors are commonly employed for the treatment of chronic myeloid leukemia, yet their impact on human malignant melanoma remains uncertain. In this study, we delved into the underlying mechanisms of specific BCR-ABL tyrosine kinase inhibitors (imatinib, nilotinib, ZM-306416, and AT-9283) in human melanoma A375P cells. We first evaluated the influence of these inhibitors on cell growth using cell proliferation and wound-healing assays. Subsequently, we scrutinized cell cycle regulation in drug-treated A375P cells using flow cytometry and Western blot assays. Notably, imatinib, nilotinib, ZM-306416, and AT-9283 significantly reduced cell proliferation and migration in A375P cells. In particular, nilotinib and AT-9283 impeded the G1/S transition of the cell cycle by down-regulating cell cycle-associated proteins, including cyclin E, cyclin A, and CDK2. Moreover, these inhibitors reduced RB phosphorylation, subsequently inhibiting E2F transcriptional activity. Consequently, the expression of the E2F target genes (CCNA2, CCNE1, POLA1, and TK-1) was markedly suppressed in nilotinib and AT9283-treated A375P cells. In summary, our findings suggest that BCR-ABL tyrosine kinase inhibitors may regulate the G1-to-S transition in human melanoma A375P cells by modulating the RB-E2F complex.

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