Iminodibenzyl induced redirected COX-2 activity inhibits breast cancer progression

Abstract Knocking down delta-5-desaturase (D5D) by siRNA or shRNA is a promising strategy to achieve 8-hydroxyoctanoic acid (8-HOA) production for cancer inhibition. However, the RNAi-based strategy to stimulate 8-HOA is restricted due to endonucleases mediated physiological degradation and off-targ...

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Autores principales:	Harshit Shah, Lizhi Pang, Steven Qian, Venkatachalem Sathish
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/f03d085c41d4413e8a48848b2bcddc17
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spelling	oai:doaj.org-article:f03d085c41d4413e8a48848b2bcddc172021-12-02T17:24:12ZIminodibenzyl induced redirected COX-2 activity inhibits breast cancer progression10.1038/s41523-021-00330-92374-4677https://doaj.org/article/f03d085c41d4413e8a48848b2bcddc172021-09-01T00:00:00Zhttps://doi.org/10.1038/s41523-021-00330-9https://doaj.org/toc/2374-4677Abstract Knocking down delta-5-desaturase (D5D) by siRNA or shRNA is a promising strategy to achieve 8-hydroxyoctanoic acid (8-HOA) production for cancer inhibition. However, the RNAi-based strategy to stimulate 8-HOA is restricted due to endonucleases mediated physiological degradation and off-target effects. Thus, to get persistent 8-HOA in the cancer cell, we recognized a D5D inhibitor Iminodibenzyl. Here, we have postulated that Iminodibenzyl, by inhibiting D5D activity, could shift the di-homo-gamma-linolenic acid (DGLA) peroxidation from arachidonic acid to 8-HOA in high COX-2 microenvironment of 4T1 and MDA-MB-231 breast cancer cells. We observed that Iminodibenzyl stimulated 8-HOA caused HDAC activity reduction resulting in intrinsic apoptosis pathway activation. Additionally, reduced filopodia and lamellipodia, and epithelial-mesenchymal transition markers give rise to decreased cancer cell migration. In the orthotopic breast cancer model, the combination of Iminodibenzyl and DGLA reduced tumor size. From in vitro and in vivo studies, we concluded that Iminodibenzyl could reprogram COX-2 induced DGLA peroxidation to produce anti-cancer activity.Harshit ShahLizhi PangSteven QianVenkatachalem SathishNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 7, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Harshit Shah Lizhi Pang Steven Qian Venkatachalem Sathish Iminodibenzyl induced redirected COX-2 activity inhibits breast cancer progression
description	Abstract Knocking down delta-5-desaturase (D5D) by siRNA or shRNA is a promising strategy to achieve 8-hydroxyoctanoic acid (8-HOA) production for cancer inhibition. However, the RNAi-based strategy to stimulate 8-HOA is restricted due to endonucleases mediated physiological degradation and off-target effects. Thus, to get persistent 8-HOA in the cancer cell, we recognized a D5D inhibitor Iminodibenzyl. Here, we have postulated that Iminodibenzyl, by inhibiting D5D activity, could shift the di-homo-gamma-linolenic acid (DGLA) peroxidation from arachidonic acid to 8-HOA in high COX-2 microenvironment of 4T1 and MDA-MB-231 breast cancer cells. We observed that Iminodibenzyl stimulated 8-HOA caused HDAC activity reduction resulting in intrinsic apoptosis pathway activation. Additionally, reduced filopodia and lamellipodia, and epithelial-mesenchymal transition markers give rise to decreased cancer cell migration. In the orthotopic breast cancer model, the combination of Iminodibenzyl and DGLA reduced tumor size. From in vitro and in vivo studies, we concluded that Iminodibenzyl could reprogram COX-2 induced DGLA peroxidation to produce anti-cancer activity.
format	article
author	Harshit Shah Lizhi Pang Steven Qian Venkatachalem Sathish
author_facet	Harshit Shah Lizhi Pang Steven Qian Venkatachalem Sathish
author_sort	Harshit Shah
title	Iminodibenzyl induced redirected COX-2 activity inhibits breast cancer progression
title_short	Iminodibenzyl induced redirected COX-2 activity inhibits breast cancer progression
title_full	Iminodibenzyl induced redirected COX-2 activity inhibits breast cancer progression
title_fullStr	Iminodibenzyl induced redirected COX-2 activity inhibits breast cancer progression
title_full_unstemmed	Iminodibenzyl induced redirected COX-2 activity inhibits breast cancer progression
title_sort	iminodibenzyl induced redirected cox-2 activity inhibits breast cancer progression
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f03d085c41d4413e8a48848b2bcddc17
work_keys_str_mv	AT harshitshah iminodibenzylinducedredirectedcox2activityinhibitsbreastcancerprogression AT lizhipang iminodibenzylinducedredirectedcox2activityinhibitsbreastcancerprogression AT stevenqian iminodibenzylinducedredirectedcox2activityinhibitsbreastcancerprogression AT venkatachalemsathish iminodibenzylinducedredirectedcox2activityinhibitsbreastcancerprogression
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Iminodibenzyl induced redirected COX-2 activity inhibits breast cancer progression

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