A Benzothiazole Derivative (5g) Induces DNA Damage And Potent G2/M Arrest In Cancer Cells

Abstract Chemically synthesized small molecules play important role in anticancer therapy. Several chemical compounds have been reported to damage the DNA, either directly or indirectly slowing down the cancer cell progression by causing a cell cycle arrest. Direct or indirect reactive oxygen specie...

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Autores principales: Mahesh Hegde, Supriya V. Vartak, Chandagirikoppal V. Kavitha, Hanumappa Ananda, Doddakunche S. Prasanna, Vidya Gopalakrishnan, Bibha Choudhary, Kanchugarakoppal S. Rangappa, Sathees C. Raghavan
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Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:d1da74c686ec4307af13114df1feb6862021-12-02T15:05:19ZA Benzothiazole Derivative (5g) Induces DNA Damage And Potent G2/M Arrest In Cancer Cells10.1038/s41598-017-02489-32045-2322https://doaj.org/article/d1da74c686ec4307af13114df1feb6862017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02489-3https://doaj.org/toc/2045-2322Abstract Chemically synthesized small molecules play important role in anticancer therapy. Several chemical compounds have been reported to damage the DNA, either directly or indirectly slowing down the cancer cell progression by causing a cell cycle arrest. Direct or indirect reactive oxygen species formation causes DNA damage leading to cell cycle arrest and subsequent cell death. Therefore, identification of chemically synthesized compounds with anticancer potential is important. Here we investigate the effect of benzothiazole derivative (5g) for its ability to inhibit cell proliferation in different cancer models. Interestingly, 5g interfered with cell proliferation in both, cell lines and tumor cells leading to significant G2/M arrest. 5g treatment resulted in elevated levels of ROS and subsequently, DNA double-strand breaks (DSBs) explaining observed G2/M arrest. Consistently, we observed deregulation of many cell cycle associated proteins such as CDK1, BCL2 and their phosphorylated form, CyclinB1, CDC25c etc. Besides, 5g treatment led to decreased levels of mitochondrial membrane potential and activation of apoptosis. Interestingly, 5g administration inhibited tumor growth in mice without significant side effects. Thus, our study identifies 5g as a potent biochemical inhibitor to induce G2/M phase arrest of the cell cycle, and demonstrates its anticancer properties both ex vivo and in vivo.Mahesh HegdeSupriya V. VartakChandagirikoppal V. KavithaHanumappa AnandaDoddakunche S. PrasannaVidya GopalakrishnanBibha ChoudharyKanchugarakoppal S. RangappaSathees C. RaghavanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Mahesh Hegde
Supriya V. Vartak
Chandagirikoppal V. Kavitha
Hanumappa Ananda
Doddakunche S. Prasanna
Vidya Gopalakrishnan
Bibha Choudhary
Kanchugarakoppal S. Rangappa
Sathees C. Raghavan
A Benzothiazole Derivative (5g) Induces DNA Damage And Potent G2/M Arrest In Cancer Cells
description Abstract Chemically synthesized small molecules play important role in anticancer therapy. Several chemical compounds have been reported to damage the DNA, either directly or indirectly slowing down the cancer cell progression by causing a cell cycle arrest. Direct or indirect reactive oxygen species formation causes DNA damage leading to cell cycle arrest and subsequent cell death. Therefore, identification of chemically synthesized compounds with anticancer potential is important. Here we investigate the effect of benzothiazole derivative (5g) for its ability to inhibit cell proliferation in different cancer models. Interestingly, 5g interfered with cell proliferation in both, cell lines and tumor cells leading to significant G2/M arrest. 5g treatment resulted in elevated levels of ROS and subsequently, DNA double-strand breaks (DSBs) explaining observed G2/M arrest. Consistently, we observed deregulation of many cell cycle associated proteins such as CDK1, BCL2 and their phosphorylated form, CyclinB1, CDC25c etc. Besides, 5g treatment led to decreased levels of mitochondrial membrane potential and activation of apoptosis. Interestingly, 5g administration inhibited tumor growth in mice without significant side effects. Thus, our study identifies 5g as a potent biochemical inhibitor to induce G2/M phase arrest of the cell cycle, and demonstrates its anticancer properties both ex vivo and in vivo.
format article
author Mahesh Hegde
Supriya V. Vartak
Chandagirikoppal V. Kavitha
Hanumappa Ananda
Doddakunche S. Prasanna
Vidya Gopalakrishnan
Bibha Choudhary
Kanchugarakoppal S. Rangappa
Sathees C. Raghavan
author_facet Mahesh Hegde
Supriya V. Vartak
Chandagirikoppal V. Kavitha
Hanumappa Ananda
Doddakunche S. Prasanna
Vidya Gopalakrishnan
Bibha Choudhary
Kanchugarakoppal S. Rangappa
Sathees C. Raghavan
author_sort Mahesh Hegde
title A Benzothiazole Derivative (5g) Induces DNA Damage And Potent G2/M Arrest In Cancer Cells
title_short A Benzothiazole Derivative (5g) Induces DNA Damage And Potent G2/M Arrest In Cancer Cells
title_full A Benzothiazole Derivative (5g) Induces DNA Damage And Potent G2/M Arrest In Cancer Cells
title_fullStr A Benzothiazole Derivative (5g) Induces DNA Damage And Potent G2/M Arrest In Cancer Cells
title_full_unstemmed A Benzothiazole Derivative (5g) Induces DNA Damage And Potent G2/M Arrest In Cancer Cells
title_sort benzothiazole derivative (5g) induces dna damage and potent g2/m arrest in cancer cells
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/d1da74c686ec4307af13114df1feb686
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