Effect of Flavopiridol on Cell Cycle, Apoptosis and Biomolecule Structure Changes in Breast Cancer Stem Cells

Objective:Cancer stem cells (CSCs) are a small population in cancer, which are responsible for therapeutic resistance, relapse and metastasis. Flavopiridol has antitumor activity against various types of cancer cells. The mechanism of action of flavopiridol on CD44+/CD24- breast CSCs has not yet bee...

Full description

Bibliographic Details
Main Authors: Eda AÇIKGÖZ, Günnur GÜLER, Gülperi ÖKTEM
Format: Article
Language:English
Published: Galenos Publishing House 2020-07-01
Series:Bezmiâlem Science
Subjects:
Online Access: http://bezmialemscience.org/archives/archive-detail/article-preview/effect-of-flavopiridol-on-cell-cycle-apoptosis-and/39953
_version_ 1797917291112824832
author Eda AÇIKGÖZ
Günnur GÜLER
Gülperi ÖKTEM
author_facet Eda AÇIKGÖZ
Günnur GÜLER
Gülperi ÖKTEM
author_sort Eda AÇIKGÖZ
collection DOAJ
description Objective:Cancer stem cells (CSCs) are a small population in cancer, which are responsible for therapeutic resistance, relapse and metastasis. Flavopiridol has antitumor activity against various types of cancer cells. The mechanism of action of flavopiridol on CD44+/CD24- breast CSCs has not yet been fully elucidated. The aim of this study was to evaluate the mechanism of action of flavopiridol on breast CSCs (BCSC) in terms of apoptosis, cell cycle and biomolecular changes.Methods:In human breast cancer, cells with CD44+/CD24− markers were isolated from MCF-7 cell line using flow cytometry. The induction of apoptosis was investigated by Annexin-V. The effect of flavopiridol on cell cycle arrest was determined and the percent of cell populations at G0/G1, S and G2/M cycles were identified. The effect of the drug on three-dimensional cell cultures was investigated using a multicellular tumor spheroid model. In addition, the effect of flavopiridol on biomolecules has been evaluated using Fourier transform infrared (FTIR) spectroscopy, which has recently been used effectively in various scientific fields.Results:Flavopiridol especially induced early apoptosis. Cell cycle analyses revealed that flavopiridol induced cell cycle arrest in G0/G1 phase. Decreased number and diameter of spheroids was observed following flavopiridol treatment. ATR-FTIR data showed that treatment with flavopiridol led to significant changes in nucleic acids.Conclusion:According to the data obtained in this study, flavopiridol exhibits anticancer effects by altering the structure/ expression level of nucleic acids and changing cell cycle progression and inducing apoptosis. These finding reveals that flavopiridol can be an effective antitumor agent for the treatment of breast cancer after in vivo and phase studies are completed.
first_indexed 2024-04-10T13:10:59Z
format Article
id doaj.art-eca4d368257c4564828f13985bf13399
institution Directory Open Access Journal
issn 2148-2373
2148-2373
language English
last_indexed 2024-04-10T13:10:59Z
publishDate 2020-07-01
publisher Galenos Publishing House
record_format Article
series Bezmiâlem Science
spelling doaj.art-eca4d368257c4564828f13985bf133992023-02-15T16:12:39ZengGalenos Publishing HouseBezmiâlem Science2148-23732148-23732020-07-018327528110.14235/bas.galenos.2019.349113049054Effect of Flavopiridol on Cell Cycle, Apoptosis and Biomolecule Structure Changes in Breast Cancer Stem CellsEda AÇIKGÖZ0Günnur GÜLER1Gülperi ÖKTEM2 Van Yüzüncü Yıl University Faculty of Medicine, Department of Medical Histology and Embryology, Van, Turkey İzmir Ekonomi University Faculty of Engineering, Department of Biomedical Engineering, İzmir, Turkey Ege University Faculty of Medicine, Department of Medical Histology and Embryology, İzmir, Turkey Objective:Cancer stem cells (CSCs) are a small population in cancer, which are responsible for therapeutic resistance, relapse and metastasis. Flavopiridol has antitumor activity against various types of cancer cells. The mechanism of action of flavopiridol on CD44+/CD24- breast CSCs has not yet been fully elucidated. The aim of this study was to evaluate the mechanism of action of flavopiridol on breast CSCs (BCSC) in terms of apoptosis, cell cycle and biomolecular changes.Methods:In human breast cancer, cells with CD44+/CD24− markers were isolated from MCF-7 cell line using flow cytometry. The induction of apoptosis was investigated by Annexin-V. The effect of flavopiridol on cell cycle arrest was determined and the percent of cell populations at G0/G1, S and G2/M cycles were identified. The effect of the drug on three-dimensional cell cultures was investigated using a multicellular tumor spheroid model. In addition, the effect of flavopiridol on biomolecules has been evaluated using Fourier transform infrared (FTIR) spectroscopy, which has recently been used effectively in various scientific fields.Results:Flavopiridol especially induced early apoptosis. Cell cycle analyses revealed that flavopiridol induced cell cycle arrest in G0/G1 phase. Decreased number and diameter of spheroids was observed following flavopiridol treatment. ATR-FTIR data showed that treatment with flavopiridol led to significant changes in nucleic acids.Conclusion:According to the data obtained in this study, flavopiridol exhibits anticancer effects by altering the structure/ expression level of nucleic acids and changing cell cycle progression and inducing apoptosis. These finding reveals that flavopiridol can be an effective antitumor agent for the treatment of breast cancer after in vivo and phase studies are completed. http://bezmialemscience.org/archives/archive-detail/article-preview/effect-of-flavopiridol-on-cell-cycle-apoptosis-and/39953 flavopiridolbreast cancercancer stem cellapoptosiscell cycleftir spectroscopy
spellingShingle Eda AÇIKGÖZ
Günnur GÜLER
Gülperi ÖKTEM
Effect of Flavopiridol on Cell Cycle, Apoptosis and Biomolecule Structure Changes in Breast Cancer Stem Cells
Bezmiâlem Science
flavopiridol
breast cancer
cancer stem cell
apoptosis
cell cycle
ftir spectroscopy
title Effect of Flavopiridol on Cell Cycle, Apoptosis and Biomolecule Structure Changes in Breast Cancer Stem Cells
title_full Effect of Flavopiridol on Cell Cycle, Apoptosis and Biomolecule Structure Changes in Breast Cancer Stem Cells
title_fullStr Effect of Flavopiridol on Cell Cycle, Apoptosis and Biomolecule Structure Changes in Breast Cancer Stem Cells
title_full_unstemmed Effect of Flavopiridol on Cell Cycle, Apoptosis and Biomolecule Structure Changes in Breast Cancer Stem Cells
title_short Effect of Flavopiridol on Cell Cycle, Apoptosis and Biomolecule Structure Changes in Breast Cancer Stem Cells
title_sort effect of flavopiridol on cell cycle apoptosis and biomolecule structure changes in breast cancer stem cells
topic flavopiridol
breast cancer
cancer stem cell
apoptosis
cell cycle
ftir spectroscopy
url http://bezmialemscience.org/archives/archive-detail/article-preview/effect-of-flavopiridol-on-cell-cycle-apoptosis-and/39953
work_keys_str_mv AT edaacikgoz effectofflavopiridoloncellcycleapoptosisandbiomoleculestructurechangesinbreastcancerstemcells
AT gunnurguler effectofflavopiridoloncellcycleapoptosisandbiomoleculestructurechangesinbreastcancerstemcells
AT gulperioktem effectofflavopiridoloncellcycleapoptosisandbiomoleculestructurechangesinbreastcancerstemcells