Mass spectrometry-based proteomic analysis to characterize cisplatin induced early signaling events in head and neck squamous cell carcinoma

Cisplatin is the commonly used chemotherapeutic drug in treatment of various cancers. However, development of resistance towards cisplatin results in tumor recurrence. Here, we aim to understand the mechanisms of action of cisplatin and emergence of resistance to cisplatin using mass spectrometry-ba...

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Main Authors: Ankit P. Jain, Vivek Ghose, Srijon Munshi, Firdous A. Bhat, Gourav Dey, Vishalakshi Nanjappa
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Molecular & Cellular Oncology
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Online Access:https://www.tandfonline.com/doi/10.1080/23723556.2024.2328873
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author Ankit P. Jain
Vivek Ghose
Srijon Munshi
Firdous A. Bhat
Gourav Dey
Vishalakshi Nanjappa
author_facet Ankit P. Jain
Vivek Ghose
Srijon Munshi
Firdous A. Bhat
Gourav Dey
Vishalakshi Nanjappa
author_sort Ankit P. Jain
collection DOAJ
description Cisplatin is the commonly used chemotherapeutic drug in treatment of various cancers. However, development of resistance towards cisplatin results in tumor recurrence. Here, we aim to understand the mechanisms of action of cisplatin and emergence of resistance to cisplatin using mass spectrometry-based proteomic approach. A panel of head and neck squamous cell carcinoma (HNSCC) cell lines were treated with cisplatin at respective IC50 for 24 h and label-free mass spectrometry analysis was carried out. Proteomic analysis of A253, FaDu, Det562 and CAL27 cell lines upon cisplatin treatment resulted in the identification of 5,060, 4,816, 4,537 and 4,142 proteins, respectively. Bioinformatics analysis of differentially regulated proteins revealed proteins implicated in DNA damage bypass pathway, translation and mRNA splicing to be enriched. Further, proteins associated with cisplatin resistance exhibited alterations following short-term cisplatin exposure. Among these, class III tubullin protein (TUBB3) was found to be upregulated in cisplatin-treated cells compared to untreated cells. Western blot analysis confirmed the elevated expression of TUBB3 in cells treated with cisplatin for 24 h, and also in cisplatin resistant HNSCC cell lines. This study delineates the early signaling events that enable HNSCC cells to counteract the cytotoxic effects of cisplatin and facilitate the development of resistance.
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spelling doaj-art-a6f31874312c4bd3a783f4a4ab77fa782025-08-20T01:58:48ZengTaylor & Francis GroupMolecular & Cellular Oncology2372-35562024-12-0111110.1080/23723556.2024.2328873Mass spectrometry-based proteomic analysis to characterize cisplatin induced early signaling events in head and neck squamous cell carcinomaAnkit P. Jain0Vivek Ghose1Srijon Munshi2Firdous A. Bhat3Gourav Dey4Vishalakshi Nanjappa5Institute of Bioinformatics, International Technology Park, Bangalore, IndiaInstitute of Bioinformatics, International Technology Park, Bangalore, IndiaInstitute of Bioinformatics, International Technology Park, Bangalore, IndiaDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USAInstitute of Bioinformatics, International Technology Park, Bangalore, IndiaInstitute of Bioinformatics, International Technology Park, Bangalore, IndiaCisplatin is the commonly used chemotherapeutic drug in treatment of various cancers. However, development of resistance towards cisplatin results in tumor recurrence. Here, we aim to understand the mechanisms of action of cisplatin and emergence of resistance to cisplatin using mass spectrometry-based proteomic approach. A panel of head and neck squamous cell carcinoma (HNSCC) cell lines were treated with cisplatin at respective IC50 for 24 h and label-free mass spectrometry analysis was carried out. Proteomic analysis of A253, FaDu, Det562 and CAL27 cell lines upon cisplatin treatment resulted in the identification of 5,060, 4,816, 4,537 and 4,142 proteins, respectively. Bioinformatics analysis of differentially regulated proteins revealed proteins implicated in DNA damage bypass pathway, translation and mRNA splicing to be enriched. Further, proteins associated with cisplatin resistance exhibited alterations following short-term cisplatin exposure. Among these, class III tubullin protein (TUBB3) was found to be upregulated in cisplatin-treated cells compared to untreated cells. Western blot analysis confirmed the elevated expression of TUBB3 in cells treated with cisplatin for 24 h, and also in cisplatin resistant HNSCC cell lines. This study delineates the early signaling events that enable HNSCC cells to counteract the cytotoxic effects of cisplatin and facilitate the development of resistance.https://www.tandfonline.com/doi/10.1080/23723556.2024.2328873Mass spectrometrydrug resistancecisplatinhead and neck cancerproteomics
spellingShingle Ankit P. Jain
Vivek Ghose
Srijon Munshi
Firdous A. Bhat
Gourav Dey
Vishalakshi Nanjappa
Mass spectrometry-based proteomic analysis to characterize cisplatin induced early signaling events in head and neck squamous cell carcinoma
Molecular & Cellular Oncology
Mass spectrometry
drug resistance
cisplatin
head and neck cancer
proteomics
title Mass spectrometry-based proteomic analysis to characterize cisplatin induced early signaling events in head and neck squamous cell carcinoma
title_full Mass spectrometry-based proteomic analysis to characterize cisplatin induced early signaling events in head and neck squamous cell carcinoma
title_fullStr Mass spectrometry-based proteomic analysis to characterize cisplatin induced early signaling events in head and neck squamous cell carcinoma
title_full_unstemmed Mass spectrometry-based proteomic analysis to characterize cisplatin induced early signaling events in head and neck squamous cell carcinoma
title_short Mass spectrometry-based proteomic analysis to characterize cisplatin induced early signaling events in head and neck squamous cell carcinoma
title_sort mass spectrometry based proteomic analysis to characterize cisplatin induced early signaling events in head and neck squamous cell carcinoma
topic Mass spectrometry
drug resistance
cisplatin
head and neck cancer
proteomics
url https://www.tandfonline.com/doi/10.1080/23723556.2024.2328873
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