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Novel SIRT1 inhibitor 15-deoxy-Δ(12,14)-prostaglandin J(2) and its derivatives exhibit anticancer activity through apoptotic or autophagic cell death pathways in SKOV3 cells

Clinically relevant sirtuin (SIRT) inhibitors may possess antitumor activities. A previous study indicated that 15-deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ(2)) exhibited potent anticancer activity by SIRT1 inhibition. Therefore, the aim of the present study was to investigate whether its derivativ...

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Autores principales: Tae, In Hwan, Park, Eun Young, Dey, Prasanta, Son, Ji Yeon, Lee, Seok-Yong, Jung, Jee h., Saloni, Saloni, Kim, Mi-Hyun, Kim, Hyung Sik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203160/
https://www.ncbi.nlm.nih.gov/pubmed/30221742
http://dx.doi.org/10.3892/ijo.2018.4561
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author Tae, In Hwan
Park, Eun Young
Dey, Prasanta
Son, Ji Yeon
Lee, Seok-Yong
Jung, Jee h.
Saloni, Saloni
Kim, Mi-Hyun
Kim, Hyung Sik
author_facet Tae, In Hwan
Park, Eun Young
Dey, Prasanta
Son, Ji Yeon
Lee, Seok-Yong
Jung, Jee h.
Saloni, Saloni
Kim, Mi-Hyun
Kim, Hyung Sik
author_sort Tae, In Hwan
collection PubMed
description Clinically relevant sirtuin (SIRT) inhibitors may possess antitumor activities. A previous study indicated that 15-deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ(2)) exhibited potent anticancer activity by SIRT1 inhibition. Therefore, the aim of the present study was to investigate whether its derivatives (J11-C1 and J19) exhibited anticancer activity against ovarian cancer SKOV3 cells. Cell viability was determined using an MTT assay. Cell cycle arrest, apoptosis and autophagy were determined using flow cytometry or western blot analysis. J11-Cl and J19 were less cytotoxic to SKOV3 cells compared with 15d-PGJ(2). Molecular docking studies supported the interactions of 15d-PGJ(2), J11-Cl and J19 with various amino acids in SIRT1 proteins. Similar to 15d-PGJ(2), J11-C1 and J19 inhibited SIRT1 enzymatic activity and decreased SIRT1 expression levels in a concentration-dependent manner. J11-C1 induced apoptotic cell death more effectively compared with J19, which was associated with markedly decreased expression of the anti-apoptotic molecule B-cell lymphoma 2 (Bcl-2). Furthermore, the levels of light chain 3-II (LC3-II) and beclin-1 were clearly induced in SKOV3 cells treated with J11-Cl. Thus, 15d-PGJ(2) and its derivatives exhibited anticancer activity possibly by inducing apoptotic or autophagic cell death pathways. Collectively, the results of the present study suggest that 15d-PGJ(2) and its derivatives exerted antitumor activity by selectively modulating the expression of genes associated with cell cycle arrest, apoptosis and autophagy. Notably, J11-C1 is a novel candidate SIRT1 inhibitor with anticancer activity.
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spelling pubmed-62031602018-11-09 Novel SIRT1 inhibitor 15-deoxy-Δ(12,14)-prostaglandin J(2) and its derivatives exhibit anticancer activity through apoptotic or autophagic cell death pathways in SKOV3 cells Tae, In Hwan Park, Eun Young Dey, Prasanta Son, Ji Yeon Lee, Seok-Yong Jung, Jee h. Saloni, Saloni Kim, Mi-Hyun Kim, Hyung Sik Int J Oncol Articles Clinically relevant sirtuin (SIRT) inhibitors may possess antitumor activities. A previous study indicated that 15-deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ(2)) exhibited potent anticancer activity by SIRT1 inhibition. Therefore, the aim of the present study was to investigate whether its derivatives (J11-C1 and J19) exhibited anticancer activity against ovarian cancer SKOV3 cells. Cell viability was determined using an MTT assay. Cell cycle arrest, apoptosis and autophagy were determined using flow cytometry or western blot analysis. J11-Cl and J19 were less cytotoxic to SKOV3 cells compared with 15d-PGJ(2). Molecular docking studies supported the interactions of 15d-PGJ(2), J11-Cl and J19 with various amino acids in SIRT1 proteins. Similar to 15d-PGJ(2), J11-C1 and J19 inhibited SIRT1 enzymatic activity and decreased SIRT1 expression levels in a concentration-dependent manner. J11-C1 induced apoptotic cell death more effectively compared with J19, which was associated with markedly decreased expression of the anti-apoptotic molecule B-cell lymphoma 2 (Bcl-2). Furthermore, the levels of light chain 3-II (LC3-II) and beclin-1 were clearly induced in SKOV3 cells treated with J11-Cl. Thus, 15d-PGJ(2) and its derivatives exhibited anticancer activity possibly by inducing apoptotic or autophagic cell death pathways. Collectively, the results of the present study suggest that 15d-PGJ(2) and its derivatives exerted antitumor activity by selectively modulating the expression of genes associated with cell cycle arrest, apoptosis and autophagy. Notably, J11-C1 is a novel candidate SIRT1 inhibitor with anticancer activity. D.A. Spandidos 2018-09-13 /pmc/articles/PMC6203160/ /pubmed/30221742 http://dx.doi.org/10.3892/ijo.2018.4561 Text en Copyright: © Tae et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Tae, In Hwan
Park, Eun Young
Dey, Prasanta
Son, Ji Yeon
Lee, Seok-Yong
Jung, Jee h.
Saloni, Saloni
Kim, Mi-Hyun
Kim, Hyung Sik
Novel SIRT1 inhibitor 15-deoxy-Δ(12,14)-prostaglandin J(2) and its derivatives exhibit anticancer activity through apoptotic or autophagic cell death pathways in SKOV3 cells
title Novel SIRT1 inhibitor 15-deoxy-Δ(12,14)-prostaglandin J(2) and its derivatives exhibit anticancer activity through apoptotic or autophagic cell death pathways in SKOV3 cells
title_full Novel SIRT1 inhibitor 15-deoxy-Δ(12,14)-prostaglandin J(2) and its derivatives exhibit anticancer activity through apoptotic or autophagic cell death pathways in SKOV3 cells
title_fullStr Novel SIRT1 inhibitor 15-deoxy-Δ(12,14)-prostaglandin J(2) and its derivatives exhibit anticancer activity through apoptotic or autophagic cell death pathways in SKOV3 cells
title_full_unstemmed Novel SIRT1 inhibitor 15-deoxy-Δ(12,14)-prostaglandin J(2) and its derivatives exhibit anticancer activity through apoptotic or autophagic cell death pathways in SKOV3 cells
title_short Novel SIRT1 inhibitor 15-deoxy-Δ(12,14)-prostaglandin J(2) and its derivatives exhibit anticancer activity through apoptotic or autophagic cell death pathways in SKOV3 cells
title_sort novel sirt1 inhibitor 15-deoxy-δ(12,14)-prostaglandin j(2) and its derivatives exhibit anticancer activity through apoptotic or autophagic cell death pathways in skov3 cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203160/
https://www.ncbi.nlm.nih.gov/pubmed/30221742
http://dx.doi.org/10.3892/ijo.2018.4561
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