Induction of mitochondria-mediated apoptosis and suppression of tumor growth in zebrafish xenograft model by cyclic dipeptides identified from Exiguobacterium acetylicum

Abstract Colorectal cancer is the most common type of gastrointestinal cancers with poor survival and limited therapeutic options. In this study, four structurally different cyclic dipeptides (or diketopiperazine) were isolated and identified as cyclo (l-Pro-l-Leu), cyclo (l-Pro-l-Val), cyclo (l-Pro...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sekar Jinendiran, Weilin Teng, Hans-Uwe Dahms, Wangta Liu, Vinoth Kumar Ponnusamy, Charles Chien-Chih Chiu, B. S. Dileep Kumar, Natesan Sivakumar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3ea8fd1054ec4ab8b0b59360c98cf452
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3ea8fd1054ec4ab8b0b59360c98cf452
record_format	dspace
spelling	oai:doaj.org-article:3ea8fd1054ec4ab8b0b59360c98cf4522021-12-02T19:06:42ZInduction of mitochondria-mediated apoptosis and suppression of tumor growth in zebrafish xenograft model by cyclic dipeptides identified from Exiguobacterium acetylicum10.1038/s41598-020-70516-x2045-2322https://doaj.org/article/3ea8fd1054ec4ab8b0b59360c98cf4522020-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-70516-xhttps://doaj.org/toc/2045-2322Abstract Colorectal cancer is the most common type of gastrointestinal cancers with poor survival and limited therapeutic options. In this study, four structurally different cyclic dipeptides (or diketopiperazine) were isolated and identified as cyclo (l-Pro-l-Leu), cyclo (l-Pro-l-Val), cyclo (l-Pro-l-Phe) and cyclo (l-Pro-l-Tyr) from the ethyl acetate extract in the cell-free filtrate of Exiguobacterium acetylicum S01. The anticancer potential of identified DKPs on colorectal cancer HT-29 cells in vitro and in vivo zebrafish xenograft model was evaluated. The MTT (3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyltetrazolium bromide)) assay showed that four DKPs exhibited significant inhibition of HT-29 cells viability in a dose-dependent manner whereas there were no cytotoxic effects on normal mouse fibroblast 3T3 cells. Also, we observed that all DKPs induce early and late apoptotic cell death in HT-29 cells. Moreover, the expression levels of apoptotic (cytochrome-c, caspase-3 and Bid) and anti-apoptotic (Bcl-2) markers were up- and down-regulated in HT-29 cells in response to DKPs treatments. Furthermore, these four DKPs remarkably inhibited the tumor progression in a zebrafish xenograft model within a nonlethal dose range. Overall, our findings suggest that cyclic dipeptides derived from E. acetylicum S01 could be promising chemopreventive/ therapeutic candidates against cancer.Sekar JinendiranWeilin TengHans-Uwe DahmsWangta LiuVinoth Kumar PonnusamyCharles Chien-Chih ChiuB. S. Dileep KumarNatesan SivakumarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-17 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sekar Jinendiran Weilin Teng Hans-Uwe Dahms Wangta Liu Vinoth Kumar Ponnusamy Charles Chien-Chih Chiu B. S. Dileep Kumar Natesan Sivakumar Induction of mitochondria-mediated apoptosis and suppression of tumor growth in zebrafish xenograft model by cyclic dipeptides identified from Exiguobacterium acetylicum
description	Abstract Colorectal cancer is the most common type of gastrointestinal cancers with poor survival and limited therapeutic options. In this study, four structurally different cyclic dipeptides (or diketopiperazine) were isolated and identified as cyclo (l-Pro-l-Leu), cyclo (l-Pro-l-Val), cyclo (l-Pro-l-Phe) and cyclo (l-Pro-l-Tyr) from the ethyl acetate extract in the cell-free filtrate of Exiguobacterium acetylicum S01. The anticancer potential of identified DKPs on colorectal cancer HT-29 cells in vitro and in vivo zebrafish xenograft model was evaluated. The MTT (3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyltetrazolium bromide)) assay showed that four DKPs exhibited significant inhibition of HT-29 cells viability in a dose-dependent manner whereas there were no cytotoxic effects on normal mouse fibroblast 3T3 cells. Also, we observed that all DKPs induce early and late apoptotic cell death in HT-29 cells. Moreover, the expression levels of apoptotic (cytochrome-c, caspase-3 and Bid) and anti-apoptotic (Bcl-2) markers were up- and down-regulated in HT-29 cells in response to DKPs treatments. Furthermore, these four DKPs remarkably inhibited the tumor progression in a zebrafish xenograft model within a nonlethal dose range. Overall, our findings suggest that cyclic dipeptides derived from E. acetylicum S01 could be promising chemopreventive/ therapeutic candidates against cancer.
format	article
author	Sekar Jinendiran Weilin Teng Hans-Uwe Dahms Wangta Liu Vinoth Kumar Ponnusamy Charles Chien-Chih Chiu B. S. Dileep Kumar Natesan Sivakumar
author_facet	Sekar Jinendiran Weilin Teng Hans-Uwe Dahms Wangta Liu Vinoth Kumar Ponnusamy Charles Chien-Chih Chiu B. S. Dileep Kumar Natesan Sivakumar
author_sort	Sekar Jinendiran
title	Induction of mitochondria-mediated apoptosis and suppression of tumor growth in zebrafish xenograft model by cyclic dipeptides identified from Exiguobacterium acetylicum
title_short	Induction of mitochondria-mediated apoptosis and suppression of tumor growth in zebrafish xenograft model by cyclic dipeptides identified from Exiguobacterium acetylicum
title_full	Induction of mitochondria-mediated apoptosis and suppression of tumor growth in zebrafish xenograft model by cyclic dipeptides identified from Exiguobacterium acetylicum
title_fullStr	Induction of mitochondria-mediated apoptosis and suppression of tumor growth in zebrafish xenograft model by cyclic dipeptides identified from Exiguobacterium acetylicum
title_full_unstemmed	Induction of mitochondria-mediated apoptosis and suppression of tumor growth in zebrafish xenograft model by cyclic dipeptides identified from Exiguobacterium acetylicum
title_sort	induction of mitochondria-mediated apoptosis and suppression of tumor growth in zebrafish xenograft model by cyclic dipeptides identified from exiguobacterium acetylicum
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/3ea8fd1054ec4ab8b0b59360c98cf452
work_keys_str_mv	AT sekarjinendiran inductionofmitochondriamediatedapoptosisandsuppressionoftumorgrowthinzebrafishxenograftmodelbycyclicdipeptidesidentifiedfromexiguobacteriumacetylicum AT weilinteng inductionofmitochondriamediatedapoptosisandsuppressionoftumorgrowthinzebrafishxenograftmodelbycyclicdipeptidesidentifiedfromexiguobacteriumacetylicum AT hansuwedahms inductionofmitochondriamediatedapoptosisandsuppressionoftumorgrowthinzebrafishxenograftmodelbycyclicdipeptidesidentifiedfromexiguobacteriumacetylicum AT wangtaliu inductionofmitochondriamediatedapoptosisandsuppressionoftumorgrowthinzebrafishxenograftmodelbycyclicdipeptidesidentifiedfromexiguobacteriumacetylicum AT vinothkumarponnusamy inductionofmitochondriamediatedapoptosisandsuppressionoftumorgrowthinzebrafishxenograftmodelbycyclicdipeptidesidentifiedfromexiguobacteriumacetylicum AT charleschienchihchiu inductionofmitochondriamediatedapoptosisandsuppressionoftumorgrowthinzebrafishxenograftmodelbycyclicdipeptidesidentifiedfromexiguobacteriumacetylicum AT bsdileepkumar inductionofmitochondriamediatedapoptosisandsuppressionoftumorgrowthinzebrafishxenograftmodelbycyclicdipeptidesidentifiedfromexiguobacteriumacetylicum AT natesansivakumar inductionofmitochondriamediatedapoptosisandsuppressionoftumorgrowthinzebrafishxenograftmodelbycyclicdipeptidesidentifiedfromexiguobacteriumacetylicum
_version_	1718377142836789248

Induction of mitochondria-mediated apoptosis and suppression of tumor growth in zebrafish xenograft model by cyclic dipeptides identified from Exiguobacterium acetylicum

Ejemplares similares