Cinobufagin Exerts Anticancer Activity in Oral Squamous Cell Carcinoma Cells through Downregulation of ANO1

Anoctamin1 (ANO1), a calcium-activated chloride channel, is frequently overexpressed in several cancers, including oral squamous cell carcinoma (OSCC). OSCC is a highly aggressive cancer and the most common oral malignancy. ANO1 has been proposed as a potential candidate for targeted anticancer ther...

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Autores principales:	Sungwoo Jo, Eunhee Yang, Yechan Lee, Dongkyu Jeon, Wan Namkung
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	cinobufagin anoctamin 1 oral squamous cell carcinoma CAL-27 STAT3 Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/3f56d5d5de6e42b3bc4e09e851a5a533
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spelling	oai:doaj.org-article:3f56d5d5de6e42b3bc4e09e851a5a5332021-11-11T17:26:12ZCinobufagin Exerts Anticancer Activity in Oral Squamous Cell Carcinoma Cells through Downregulation of ANO110.3390/ijms2221120371422-00671661-6596https://doaj.org/article/3f56d5d5de6e42b3bc4e09e851a5a5332021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/12037https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Anoctamin1 (ANO1), a calcium-activated chloride channel, is frequently overexpressed in several cancers, including oral squamous cell carcinoma (OSCC). OSCC is a highly aggressive cancer and the most common oral malignancy. ANO1 has been proposed as a potential candidate for targeted anticancer therapy. In this study, we performed a cell-based screening to identify novel regulators leading to the downregulation of ANO1, and discovered cinobufagin, which downregulated ANO1 expression in oral squamous cell carcinoma CAL-27 cells. ANO1 protein levels were significantly reduced by cinobufagin in a dose-dependent manner with an IC<sub>50</sub> value of ~26 nM. Unlike previous ANO1 inhibitors, short-term (≤10 min) exposure to cinobufagin did not alter ANO1 chloride channel activity and ANO1-dependent intestinal smooth muscle contraction, whereas long-term (24 h) exposure to cinobufagin significantly reduced phosphorylation of STAT3 and mRNA expression of ANO1 in CAL-27 cells. Notably, cinobufagin inhibited cell proliferation of CAL-27 cells expressing high levels of ANO1 more potently than that of ANO1 knockout CAL-27 cells. In addition, cinobufagin significantly reduced cell migration and induced caspase-3 activation and PARP cleavage in CAL-27 cells. These results suggest that downregulation of ANO1 by cinobufagin is a potential mechanism for the anticancer effect of cinobufagin in OSCC.Sungwoo JoEunhee YangYechan LeeDongkyu JeonWan NamkungMDPI AGarticlecinobufaginanoctamin 1oral squamous cell carcinomaCAL-27STAT3Biology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12037, p 12037 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cinobufagin anoctamin 1 oral squamous cell carcinoma CAL-27 STAT3 Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	cinobufagin anoctamin 1 oral squamous cell carcinoma CAL-27 STAT3 Biology (General) QH301-705.5 Chemistry QD1-999 Sungwoo Jo Eunhee Yang Yechan Lee Dongkyu Jeon Wan Namkung Cinobufagin Exerts Anticancer Activity in Oral Squamous Cell Carcinoma Cells through Downregulation of ANO1
description	Anoctamin1 (ANO1), a calcium-activated chloride channel, is frequently overexpressed in several cancers, including oral squamous cell carcinoma (OSCC). OSCC is a highly aggressive cancer and the most common oral malignancy. ANO1 has been proposed as a potential candidate for targeted anticancer therapy. In this study, we performed a cell-based screening to identify novel regulators leading to the downregulation of ANO1, and discovered cinobufagin, which downregulated ANO1 expression in oral squamous cell carcinoma CAL-27 cells. ANO1 protein levels were significantly reduced by cinobufagin in a dose-dependent manner with an IC<sub>50</sub> value of ~26 nM. Unlike previous ANO1 inhibitors, short-term (≤10 min) exposure to cinobufagin did not alter ANO1 chloride channel activity and ANO1-dependent intestinal smooth muscle contraction, whereas long-term (24 h) exposure to cinobufagin significantly reduced phosphorylation of STAT3 and mRNA expression of ANO1 in CAL-27 cells. Notably, cinobufagin inhibited cell proliferation of CAL-27 cells expressing high levels of ANO1 more potently than that of ANO1 knockout CAL-27 cells. In addition, cinobufagin significantly reduced cell migration and induced caspase-3 activation and PARP cleavage in CAL-27 cells. These results suggest that downregulation of ANO1 by cinobufagin is a potential mechanism for the anticancer effect of cinobufagin in OSCC.
format	article
author	Sungwoo Jo Eunhee Yang Yechan Lee Dongkyu Jeon Wan Namkung
author_facet	Sungwoo Jo Eunhee Yang Yechan Lee Dongkyu Jeon Wan Namkung
author_sort	Sungwoo Jo
title	Cinobufagin Exerts Anticancer Activity in Oral Squamous Cell Carcinoma Cells through Downregulation of ANO1
title_short	Cinobufagin Exerts Anticancer Activity in Oral Squamous Cell Carcinoma Cells through Downregulation of ANO1
title_full	Cinobufagin Exerts Anticancer Activity in Oral Squamous Cell Carcinoma Cells through Downregulation of ANO1
title_fullStr	Cinobufagin Exerts Anticancer Activity in Oral Squamous Cell Carcinoma Cells through Downregulation of ANO1
title_full_unstemmed	Cinobufagin Exerts Anticancer Activity in Oral Squamous Cell Carcinoma Cells through Downregulation of ANO1
title_sort	cinobufagin exerts anticancer activity in oral squamous cell carcinoma cells through downregulation of ano1
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/3f56d5d5de6e42b3bc4e09e851a5a533
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Cinobufagin Exerts Anticancer Activity in Oral Squamous Cell Carcinoma Cells through Downregulation of ANO1

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