Palbociclib induces DNA damage and inhibits DNA repair to induce cellular senescence and apoptosis in oral squamous cell carcinoma
Open accessAbstract
BACKGROUND/PURPOSE: Palbociclib is an FDA-approved cyclin-dependent kinase (CDK) 4/6 inhibitor that has been clinically proven to be effective in breast cancer. However, its use in oral cancer is not well researched. In this study, we investigated the inhibitory activity of palbociclib against oral squamous cell carcinoma (OSCC) cells and explored the mechanism of inhibition. METHODS: The effects of palbociclib on the cytotoxicity of OSCC cells were determined by MTT and colony formation assays. β-Galactosidase staining and cell-cycle analysis were used to determine palbociclib-induced cellular senescence and apoptosis of OSCC cells. Wound healing and transwell assays were performed to assess the effects of palbociclib treatment on migration and invasion ability of OSCC cells. Whole transcriptome sequencing was conducted to show the relationship between DNA damage repair of OSCC cells and palbociclib treatment. Palbociclib-induced DNA damage and repair capacity of OSCC cells were confirmed by comet assay and immunofluorescence confocal microscopy. Western blotting was used to verify the palbociclib-mediated changes in the CDK/pRB/c-Myc/CDC25A pathway. Finally, in vitro findings were tested in a mouse xenograft model. RESULTS: Our results showed that palbociclib can significantly inhibit the growth, migration, and invasive ability of OSCC cells and can accelerate cellular senescence and apoptosis. We found that palbociclib induced DNA damage and p21 expression through the p53-independent pathway, thereby downregulating c-Myc and CDC25A expression to inhibit cell cycle progression. In addition, palbociclib downregulated RAD51 expression to inhibit DNA damage repair ability of OSCC cell. CONCLUSION: Palbociclib was found to have anti-oral squamous cell carcinoma activity and to simultaneously induce DNA damage and inhibit its repair, and to accelerated cellular senescence and apoptosis.
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Treatment of melanoma cells with Palbociclib leads to cell cycle arrest at the G0/G1 phase, accompanied by SA-βgal and SASP that includes factors such as IL-6, IL-8, and CXCL1.
“Similarly, treatment of melanoma cells with Palbociclib leads to cell cycle arrest at the G0/G1 phase, accompanied by SA-βgal and SASP that includes factors such as IL-6, IL-8, and CXCL1.290”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [290]
The section on OSCC cell growth and senescence (page not provided) reports that palbociclib-treated oral squamous cell carcinoma cells remained mostly in G1 and showed increased SA-βgal. The cited results concern OSCC cells, not melanoma cells, and the passages do not report a SASP containing IL-6, IL-8, or CXCL1. (LLM, conf=0.88)
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“Furthermore, these senescent cells exhibit elevated levels of proinflammatory cytokines like IL-6, IL-17, and TNF-α, along with reduced levels of the anti-inflammatory cytokine IL-4, indicating the presence of inflammation.289 Similarly, treatment of melanoma cells with Palbociclib leads to cell cycle arrest at the G0…”
BackgroundThe Cancer SENESCopedia: A delineation of cancer cell senescence
Jochems, F., Thijssen, B., De Conti, G., Jansen, R., Pogacar, Z., Groot, K., Wang, L., Schepers, A., Wang, C., Jin, H., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109441 · Cited by 201 · see citing works
- Authors
- Wang, T.-H., Chen, C.-C., Leu, Y.-L., Lee, Y.-S., Lian, J.-H., Hsieh, H.-L., & Chen, C.-Y.
- Affiliations
- Chang Gung University of Science and Technology (TW)
- Chang Gung University (TW)
- Ming Chuan University (TW)
- Chang Gung Memorial Hospital (TW)
- Corresponding author
- Hsieh, Hsi-Lung
- Chen, Chi-Yuan
- Venue
- Journal of the Formosan Medical Association
- Publisher
- Elsevier BV
- Published
- 2021-09
- Volume
- 120
- Issue
- 9
- Pages
- 1695-1705
- ISSN
- 0929-6646 (ISSN-L)
- OpenAlex
- W3111987130
- Cited by
- 49
- References
- 46
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 15 · 2023: 5 · 2022: 7 · 2021: 7
- FWCI
- 3.83
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of the Formosan Medical Association (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Chang Gung Memorial Hospital
- Chang Gung Medical Foundation (CMRPF1H0013, CMRPG3J0862)
- Ministry of Science and Technology, Taiwan (MOST 107-2320-B255-0)
- Changchun University of Science and Technology (ZRRPF3K0111)
- Topics
- Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Advanced Breast Cancer Therapies
- Keywords
- palbociclib, oral squamous cell carcinoma, CDK4/6 inhibitors, cellular senescence, apoptosis, DNA damage, DNA repair, RAD51, p21, c-Myc, CDC25A, retinoblastoma protein, cell migration and invasion, xenograft models
- MeSH terms
- Squamous Cell Carcinoma of Head and Neck, Animals, Carcinoma, Squamous Cell, DNA Damage, DNA Repair, Head and Neck Neoplasms, Mouth Neoplasms, Piperazines, Pyridines, Cellular Senescence, Apoptosis, Cell Line, Tumor, Cell Proliferation, Mice
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