Vibrational spectroscopy unveils distinct cell cycle features of cancer stem cells in melanoma

Abstract Cancer stem cells (CSCs) play a central role in melanoma growth, resistance to treatment, and relapse, however, their dynamic regulatory behavior remains poorly understood. Vibrational spectroscopy offers a unique, label-free approach to investigate cellular heterogeneity at the molecular l...

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Main Authors: Bensu Rüya Uslu, Berrin Ozdil, Enver Tarhan, Serdar Özçelik, Hüseyin Aktuğ, Günnur Güler
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-14018-8
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author Bensu Rüya Uslu
Berrin Ozdil
Enver Tarhan
Serdar Özçelik
Hüseyin Aktuğ
Günnur Güler
author_facet Bensu Rüya Uslu
Berrin Ozdil
Enver Tarhan
Serdar Özçelik
Hüseyin Aktuğ
Günnur Güler
author_sort Bensu Rüya Uslu
collection DOAJ
description Abstract Cancer stem cells (CSCs) play a central role in melanoma growth, resistance to treatment, and relapse, however, their dynamic regulatory behavior remains poorly understood. Vibrational spectroscopy offers a unique, label-free approach to investigate cellular heterogeneity at the molecular level. Here, we explored the biochemical and regulatory dynamics of CSCs identified by using a time-course design, integrating infrared and Raman spectroscopies with cell cycle analysis and immunocytochemistry targeting the checkpoint proteins p16 and p21. CSCs, non-cancer stem cells (NCSCs), and bulk CHL-1 melanoma cells were monitored at 11, 24, 48, and 72 h. CSCs showed a steady S-phase with an early rise in p16 followed by a subsequent increase in p21 expression, indicating a dynamic state of cell cycle checkpoints. In contrast, NCSCs and CHL-1 cells showed more transient p16/p21 expression and CHL-1 exhibited a marked p16 increase at 24 h. Spectroscopic analysis revealed that CSCs exhibited distinct vibrational profiles, predominantly in the nucleic acid-, protein- and lipid-associated regions. These differences were further supported by principal component and hierarchical clustering analyses, which consistently distinguished CSCs from NCSCs. Our findings underline the potential of vibrational spectroscopy to sensitively detect CSC-specific regulatory patterns and support its use in detecting new therapeutic targets in melanoma.
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spelling doaj-art-1a3059441a194f8e8a1d5ddeea94c96f2025-08-20T03:42:33ZengNature PortfolioScientific Reports2045-23222025-08-0115111310.1038/s41598-025-14018-8Vibrational spectroscopy unveils distinct cell cycle features of cancer stem cells in melanomaBensu Rüya Uslu0Berrin Ozdil1Enver Tarhan2Serdar Özçelik3Hüseyin Aktuğ4Günnur Güler5Department of Physics, Faculty of Science, İzmir Institute of TechnologyDepartment of Physics, Faculty of Science, İzmir Institute of TechnologyDepartment of Physics, Faculty of Science, İzmir Institute of TechnologyDepartment of Chemistry, Faculty of Science, İzmir Institute of TechnologyFaculty of Medicine, Department of Histology and Embryology, Ege UniversityDepartment of Physics, Faculty of Science, İzmir Institute of TechnologyAbstract Cancer stem cells (CSCs) play a central role in melanoma growth, resistance to treatment, and relapse, however, their dynamic regulatory behavior remains poorly understood. Vibrational spectroscopy offers a unique, label-free approach to investigate cellular heterogeneity at the molecular level. Here, we explored the biochemical and regulatory dynamics of CSCs identified by using a time-course design, integrating infrared and Raman spectroscopies with cell cycle analysis and immunocytochemistry targeting the checkpoint proteins p16 and p21. CSCs, non-cancer stem cells (NCSCs), and bulk CHL-1 melanoma cells were monitored at 11, 24, 48, and 72 h. CSCs showed a steady S-phase with an early rise in p16 followed by a subsequent increase in p21 expression, indicating a dynamic state of cell cycle checkpoints. In contrast, NCSCs and CHL-1 cells showed more transient p16/p21 expression and CHL-1 exhibited a marked p16 increase at 24 h. Spectroscopic analysis revealed that CSCs exhibited distinct vibrational profiles, predominantly in the nucleic acid-, protein- and lipid-associated regions. These differences were further supported by principal component and hierarchical clustering analyses, which consistently distinguished CSCs from NCSCs. Our findings underline the potential of vibrational spectroscopy to sensitively detect CSC-specific regulatory patterns and support its use in detecting new therapeutic targets in melanoma.https://doi.org/10.1038/s41598-025-14018-8Cancer stem cellsMalignant melanomaCell cycleInfrared spectroscopy, raman spectroscopyMultivariate analysis
spellingShingle Bensu Rüya Uslu
Berrin Ozdil
Enver Tarhan
Serdar Özçelik
Hüseyin Aktuğ
Günnur Güler
Vibrational spectroscopy unveils distinct cell cycle features of cancer stem cells in melanoma
Scientific Reports
Cancer stem cells
Malignant melanoma
Cell cycle
Infrared spectroscopy, raman spectroscopy
Multivariate analysis
title Vibrational spectroscopy unveils distinct cell cycle features of cancer stem cells in melanoma
title_full Vibrational spectroscopy unveils distinct cell cycle features of cancer stem cells in melanoma
title_fullStr Vibrational spectroscopy unveils distinct cell cycle features of cancer stem cells in melanoma
title_full_unstemmed Vibrational spectroscopy unveils distinct cell cycle features of cancer stem cells in melanoma
title_short Vibrational spectroscopy unveils distinct cell cycle features of cancer stem cells in melanoma
title_sort vibrational spectroscopy unveils distinct cell cycle features of cancer stem cells in melanoma
topic Cancer stem cells
Malignant melanoma
Cell cycle
Infrared spectroscopy, raman spectroscopy
Multivariate analysis
url https://doi.org/10.1038/s41598-025-14018-8
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