Aspirin and Sulindac act via different mechanisms to inhibit store-operated calcium channel: Implications for colorectal cancer metastasis

Store-operated Ca2+ channel (SOC)-regulated Ca2+ entry is involved in inflammation and colorectal cancer (CRC) progression, but clinically applicable treatments targeting this mechanism are lacking. Recent studies have shown that nonsteroidal anti-inflammatory drugs (NSAIDs) not only inhibit inflamm...

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Autores principales:	Yu-Shiuan Wang, Nai-Kuei Huang, Yu-Chiao Lin, Wei-Chiao Chang, Wan-Chen Huang
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	NSAID Aspirin Sulindac Calcium SOC Colorectal cancer Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/7d2115d68a7c43f58e0b8f5a8e3c4e8e
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spelling	oai:doaj.org-article:7d2115d68a7c43f58e0b8f5a8e3c4e8e2021-12-02T04:59:08ZAspirin and Sulindac act via different mechanisms to inhibit store-operated calcium channel: Implications for colorectal cancer metastasis0753-332210.1016/j.biopha.2021.112476https://doaj.org/article/7d2115d68a7c43f58e0b8f5a8e3c4e8e2022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0753332221012622https://doaj.org/toc/0753-3322Store-operated Ca2+ channel (SOC)-regulated Ca2+ entry is involved in inflammation and colorectal cancer (CRC) progression, but clinically applicable treatments targeting this mechanism are lacking. Recent studies have shown that nonsteroidal anti-inflammatory drugs (NSAIDs) not only inhibit inflammation but they also suppress Ca2+ entry via SOC (SOCE). Therefore, delineating the mechanisms of SOCE inhibition by NSAIDs may lead to new CRC treatments. In this study, we tested eight candidate NSAIDs in Ca2+ imaging experiments and found that Aspirin and Sulindac were the most effective at suppressing SOCE. Furthermore, time-lapse FRET imaging using TIRF microscopy and ground state depletion (GSD) super-resolution (SR) imaging revealed that SOC was inhibited by Aspirin and Sulindac via different mechanisms. Aspirin quickly interrupted the STIM1-Orai1 interaction, whereas Sulindac mainly suppressed STIM1 translocation. Additionally, Aspirin and Sulindac both inhibited metastasis-related endpoints in CRC cells. Both drugs were used throughout the study at doses that suppressed CRC cell migration and invasion without altering cell survival. This is the first study to reveal the differential inhibitory mechanisms of Aspirin and Sulindac on SOC activity. Thus, our results shed new light on the therapeutic potential of Aspirin for CRC and SOCE-related diseases.Yu-Shiuan WangNai-Kuei HuangYu-Chiao LinWei-Chiao ChangWan-Chen HuangElsevierarticleNSAIDAspirinSulindacCalciumSOCColorectal cancerTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 145, Iss , Pp 112476- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	NSAID Aspirin Sulindac Calcium SOC Colorectal cancer Therapeutics. Pharmacology RM1-950
spellingShingle	NSAID Aspirin Sulindac Calcium SOC Colorectal cancer Therapeutics. Pharmacology RM1-950 Yu-Shiuan Wang Nai-Kuei Huang Yu-Chiao Lin Wei-Chiao Chang Wan-Chen Huang Aspirin and Sulindac act via different mechanisms to inhibit store-operated calcium channel: Implications for colorectal cancer metastasis
description	Store-operated Ca2+ channel (SOC)-regulated Ca2+ entry is involved in inflammation and colorectal cancer (CRC) progression, but clinically applicable treatments targeting this mechanism are lacking. Recent studies have shown that nonsteroidal anti-inflammatory drugs (NSAIDs) not only inhibit inflammation but they also suppress Ca2+ entry via SOC (SOCE). Therefore, delineating the mechanisms of SOCE inhibition by NSAIDs may lead to new CRC treatments. In this study, we tested eight candidate NSAIDs in Ca2+ imaging experiments and found that Aspirin and Sulindac were the most effective at suppressing SOCE. Furthermore, time-lapse FRET imaging using TIRF microscopy and ground state depletion (GSD) super-resolution (SR) imaging revealed that SOC was inhibited by Aspirin and Sulindac via different mechanisms. Aspirin quickly interrupted the STIM1-Orai1 interaction, whereas Sulindac mainly suppressed STIM1 translocation. Additionally, Aspirin and Sulindac both inhibited metastasis-related endpoints in CRC cells. Both drugs were used throughout the study at doses that suppressed CRC cell migration and invasion without altering cell survival. This is the first study to reveal the differential inhibitory mechanisms of Aspirin and Sulindac on SOC activity. Thus, our results shed new light on the therapeutic potential of Aspirin for CRC and SOCE-related diseases.
format	article
author	Yu-Shiuan Wang Nai-Kuei Huang Yu-Chiao Lin Wei-Chiao Chang Wan-Chen Huang
author_facet	Yu-Shiuan Wang Nai-Kuei Huang Yu-Chiao Lin Wei-Chiao Chang Wan-Chen Huang
author_sort	Yu-Shiuan Wang
title	Aspirin and Sulindac act via different mechanisms to inhibit store-operated calcium channel: Implications for colorectal cancer metastasis
title_short	Aspirin and Sulindac act via different mechanisms to inhibit store-operated calcium channel: Implications for colorectal cancer metastasis
title_full	Aspirin and Sulindac act via different mechanisms to inhibit store-operated calcium channel: Implications for colorectal cancer metastasis
title_fullStr	Aspirin and Sulindac act via different mechanisms to inhibit store-operated calcium channel: Implications for colorectal cancer metastasis
title_full_unstemmed	Aspirin and Sulindac act via different mechanisms to inhibit store-operated calcium channel: Implications for colorectal cancer metastasis
title_sort	aspirin and sulindac act via different mechanisms to inhibit store-operated calcium channel: implications for colorectal cancer metastasis
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/7d2115d68a7c43f58e0b8f5a8e3c4e8e
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Aspirin and Sulindac act via different mechanisms to inhibit store-operated calcium channel: Implications for colorectal cancer metastasis

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