Modulation of Chemotherapy Sensitivity of Breast Cancer Cells through Transforming Growth Factor-beta Pathway-mediated Alterations in DNA Damage Response Article Swipe
Abdullah S. Alhamed
,
Mohammad S. El‐Wetidy
,
Mohamed Abdelwahed
,
Sabry M. Attia
,
Abdulrahman M Alabkka
,
Saleh A Alaraj
,
Khalid Alhazzani
,
Ahmed Z. Alanazi
,
Faris Almutairi
,
Ibrahem A Alotibi
,
Mohammed Alqinyah
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.7150/ijms.111217
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.7150/ijms.111217
Chemotherapeutic drugs, like cisplatin, function by damaging genomic DNA, thus inducing cell apoptosis. Cancer cells can enhance their DNA repair capacity, leading to chemotherapeutic resistance. Nucleotide excision repair (NER) involves repairing DNA adducts and crosslinks caused by chemotherapeutic agents. Transforming growth factor-beta (TGF-β) pathway contributes to carcinogenesis, DNA repair alteration, and chemoresistance. However, the connection between TGF-β pathway, NER function alteration, and resistance to cisplatin therapy remains elusive. Therefore, the objective of current study was to fill this gap by assessing the impact of TGF-β inhibition and activation on cisplatin-induced antiproliferation, apoptosis, and DNA damage using the MTT assay, flow cytometry analysis, and COMET assay, respectively. Four NER genes, XPA, XPB, XPC, and XPF, were measured using Real-time Polymerase Chain Reaction (qPCR). MDA-MB-231 cell line was utilized as a model of breast cancer. Blockade of the TGF-β pathway strengthened cisplatin cytotoxicity, whereas induction of the TGF-β pathway suppressed cisplatin cytotoxicity. In cisplatin-treated breast cancer cells, DNA damage significantly increased upon the TGF-β pathway inhibition. Conversely, cisplatin-induced DNA damage decreased significantly upon TGF-β pathway stimulation. Finally, cisplatin caused an overexpression of the four NER genes which was curtailed and augmented by TGF-β inhibition and stimulation, respectively. Overall, this study presented evidence of the impact exerted by TGF-β pathway on NER and cisplatin sensitivity of breast cancer cells.
Related Topics
Concepts
Transforming growth factor beta
Chemotherapy
DNA damage
BETA (programming language)
Cancer research
Breast cancer
Sensitivity (control systems)
Oncology
Medicine
Internal medicine
Transforming growth factor
DNA
Cancer
Biology
Genetics
Computer science
Electronic engineering
Engineering
Programming language
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.7150/ijms.111217
- https://www.medsci.org/v22p2031.pdf
- OA Status
- gold
- References
- 3
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4409300663
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4409300663Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.7150/ijms.111217Digital Object Identifier
- Title
-
Modulation of Chemotherapy Sensitivity of Breast Cancer Cells through Transforming Growth Factor-beta Pathway-mediated Alterations in DNA Damage ResponseWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-03-31Full publication date if available
- Authors
-
Abdullah S. Alhamed, Mohammad S. El‐Wetidy, Mohamed Abdelwahed, Sabry M. Attia, Abdulrahman M Alabkka, Saleh A Alaraj, Khalid Alhazzani, Ahmed Z. Alanazi, Faris Almutairi, Ibrahem A Alotibi, Mohammed AlqinyahList of authors in order
- Landing page
-
https://doi.org/10.7150/ijms.111217Publisher landing page
- PDF URL
-
https://www.medsci.org/v22p2031.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.medsci.org/v22p2031.pdfDirect OA link when available
- Concepts
-
Transforming growth factor beta, Chemotherapy, DNA damage, BETA (programming language), Cancer research, Breast cancer, Sensitivity (control systems), Oncology, Medicine, Internal medicine, Transforming growth factor, DNA, Cancer, Biology, Genetics, Computer science, Electronic engineering, Engineering, Programming languageTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
0Total citation count in OpenAlex
- References (count)
-
3Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.Finally, | 174 |
| abstract_inverted_index.However, | 52 |
| abstract_inverted_index.Overall, | 195 |
| abstract_inverted_index.Reaction | 120 |
| abstract_inverted_index.damaging | 6 |
| abstract_inverted_index.elusive. | 67 |
| abstract_inverted_index.evidence | 199 |
| abstract_inverted_index.excision | 26 |
| abstract_inverted_index.function | 4, 59 |
| abstract_inverted_index.inducing | 10 |
| abstract_inverted_index.involves | 29 |
| abstract_inverted_index.measured | 115 |
| abstract_inverted_index.pathway, | 57 |
| abstract_inverted_index.utilized | 126 |
| abstract_inverted_index.Real-time | 117 |
| abstract_inverted_index.analysis, | 101 |
| abstract_inverted_index.assessing | 80 |
| abstract_inverted_index.augmented | 188 |
| abstract_inverted_index.capacity, | 20 |
| abstract_inverted_index.cisplatin | 64, 139, 148, 175, 210 |
| abstract_inverted_index.curtailed | 186 |
| abstract_inverted_index.cytometry | 100 |
| abstract_inverted_index.decreased | 168 |
| abstract_inverted_index.increased | 158 |
| abstract_inverted_index.induction | 142 |
| abstract_inverted_index.objective | 70 |
| abstract_inverted_index.presented | 198 |
| abstract_inverted_index.repairing | 30 |
| abstract_inverted_index.MDA-MB-231 | 122 |
| abstract_inverted_index.Nucleotide | 25 |
| abstract_inverted_index.Polymerase | 118 |
| abstract_inverted_index.Therefore, | 68 |
| abstract_inverted_index.activation | 87 |
| abstract_inverted_index.apoptosis, | 91 |
| abstract_inverted_index.apoptosis. | 12 |
| abstract_inverted_index.cisplatin, | 3 |
| abstract_inverted_index.connection | 54 |
| abstract_inverted_index.crosslinks | 34 |
| abstract_inverted_index.inhibition | 85, 191 |
| abstract_inverted_index.resistance | 62 |
| abstract_inverted_index.suppressed | 147 |
| abstract_inverted_index.Conversely, | 164 |
| abstract_inverted_index.alteration, | 49, 60 |
| abstract_inverted_index.contributes | 44 |
| abstract_inverted_index.factor-beta | 41 |
| abstract_inverted_index.inhibition. | 163 |
| abstract_inverted_index.resistance. | 24 |
| abstract_inverted_index.sensitivity | 211 |
| abstract_inverted_index.Transforming | 39 |
| abstract_inverted_index.stimulation, | 193 |
| abstract_inverted_index.stimulation. | 173 |
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| abstract_inverted_index.cytotoxicity. | 149 |
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| abstract_inverted_index.Chemotherapeutic | 0 |
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| abstract_inverted_index.chemotherapeutic | 23, 37 |
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| abstract_inverted_index.cisplatin-treated | 151 |
| abstract_inverted_index.antiproliferation, | 90 |
| cited_by_percentile_year | |
| countries_distinct_count | 1 |
| institutions_distinct_count | 11 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.7200000286102295 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.16379115 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |