Luteolin Inhibits Breast Cancer Stemness and Enhances Chemosensitivity through the Nrf2-Mediated Pathway

Cancer stem cells (CSCs) are subpopulations of tumor masses with unique abilities in self-renewal, stemness maintenance, drug resistance, and the promotion of cancer recurrence. Recent studies have suggested that breast CSCs play essential roles in chemoresistance. Therefore, new agents that selecti...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Kuen-Jang Tsai, Hsin-Yi Tsai, Chin-Chuan Tsai, Tai-Yu Chen, Tsung-Hua Hsieh, Chun-Lin Chen, Lulekiwe Mbuyisa, Yaw-Bin Huang, Ming-Wei Lin
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	luteolin breast cancer cancer stemness chemosensitivity Nrf2 Cripto-1 Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/2613cc7450ad4f43a9ab4a40100bedae
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:2613cc7450ad4f43a9ab4a40100bedae
record_format	dspace
spelling	oai:doaj.org-article:2613cc7450ad4f43a9ab4a40100bedae2021-11-11T18:28:05ZLuteolin Inhibits Breast Cancer Stemness and Enhances Chemosensitivity through the Nrf2-Mediated Pathway10.3390/molecules262164521420-3049https://doaj.org/article/2613cc7450ad4f43a9ab4a40100bedae2021-10-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6452https://doaj.org/toc/1420-3049Cancer stem cells (CSCs) are subpopulations of tumor masses with unique abilities in self-renewal, stemness maintenance, drug resistance, and the promotion of cancer recurrence. Recent studies have suggested that breast CSCs play essential roles in chemoresistance. Therefore, new agents that selectively target such cells are urgently required. Reactive oxygen species (ROS)-producing enzymes are the reason for an elevated tumor oxidant status. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcriptional factor, which upon detecting cellular oxidative stress, binds to the promoter region of antioxidant genes. By triggering a cytoprotective response, Nrf2 maintains cellular redox status. Cripto-1 participates in the self-renewal of CSCs. Herein, luteolin, a flavonoid found in <i>Taraxacum</i> <i>officinale</i> extract, was determined to inhibit the expressions of stemness-related transcriptional factors, the ATP-binding cassette transporter G2 (ABCG2), CD44, aldehyde dehydrogenase 1 activity as well as the sphere formation properties of breast CSCs. Furthermore, luteolin suppressed the protein expressions of Nrf2, heme oxygenase 1 (HO-1), and Cripto-1 which have been determined to contribute critically to CSC features. The combination of luteolin and the chemotherapeutic drug, Taxol, resulted in enhanced cytotoxicity to breast cancer cells. These findings suggest that luteolin treatment significantly attenuated the hallmarks of breast cancer stemness by downregulating Nrf2-mediated expressions. Luteolin constitutes a potential agent for use in cancer stemness-targeted breast cancer treatments.Kuen-Jang TsaiHsin-Yi TsaiChin-Chuan TsaiTai-Yu ChenTsung-Hua HsiehChun-Lin ChenLulekiwe MbuyisaYaw-Bin HuangMing-Wei LinMDPI AGarticleluteolinbreast cancercancer stemnesschemosensitivityNrf2Cripto-1Organic chemistryQD241-441ENMolecules, Vol 26, Iss 6452, p 6452 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	luteolin breast cancer cancer stemness chemosensitivity Nrf2 Cripto-1 Organic chemistry QD241-441
spellingShingle	luteolin breast cancer cancer stemness chemosensitivity Nrf2 Cripto-1 Organic chemistry QD241-441 Kuen-Jang Tsai Hsin-Yi Tsai Chin-Chuan Tsai Tai-Yu Chen Tsung-Hua Hsieh Chun-Lin Chen Lulekiwe Mbuyisa Yaw-Bin Huang Ming-Wei Lin Luteolin Inhibits Breast Cancer Stemness and Enhances Chemosensitivity through the Nrf2-Mediated Pathway
description	Cancer stem cells (CSCs) are subpopulations of tumor masses with unique abilities in self-renewal, stemness maintenance, drug resistance, and the promotion of cancer recurrence. Recent studies have suggested that breast CSCs play essential roles in chemoresistance. Therefore, new agents that selectively target such cells are urgently required. Reactive oxygen species (ROS)-producing enzymes are the reason for an elevated tumor oxidant status. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcriptional factor, which upon detecting cellular oxidative stress, binds to the promoter region of antioxidant genes. By triggering a cytoprotective response, Nrf2 maintains cellular redox status. Cripto-1 participates in the self-renewal of CSCs. Herein, luteolin, a flavonoid found in <i>Taraxacum</i> <i>officinale</i> extract, was determined to inhibit the expressions of stemness-related transcriptional factors, the ATP-binding cassette transporter G2 (ABCG2), CD44, aldehyde dehydrogenase 1 activity as well as the sphere formation properties of breast CSCs. Furthermore, luteolin suppressed the protein expressions of Nrf2, heme oxygenase 1 (HO-1), and Cripto-1 which have been determined to contribute critically to CSC features. The combination of luteolin and the chemotherapeutic drug, Taxol, resulted in enhanced cytotoxicity to breast cancer cells. These findings suggest that luteolin treatment significantly attenuated the hallmarks of breast cancer stemness by downregulating Nrf2-mediated expressions. Luteolin constitutes a potential agent for use in cancer stemness-targeted breast cancer treatments.
format	article
author	Kuen-Jang Tsai Hsin-Yi Tsai Chin-Chuan Tsai Tai-Yu Chen Tsung-Hua Hsieh Chun-Lin Chen Lulekiwe Mbuyisa Yaw-Bin Huang Ming-Wei Lin
author_facet	Kuen-Jang Tsai Hsin-Yi Tsai Chin-Chuan Tsai Tai-Yu Chen Tsung-Hua Hsieh Chun-Lin Chen Lulekiwe Mbuyisa Yaw-Bin Huang Ming-Wei Lin
author_sort	Kuen-Jang Tsai
title	Luteolin Inhibits Breast Cancer Stemness and Enhances Chemosensitivity through the Nrf2-Mediated Pathway
title_short	Luteolin Inhibits Breast Cancer Stemness and Enhances Chemosensitivity through the Nrf2-Mediated Pathway
title_full	Luteolin Inhibits Breast Cancer Stemness and Enhances Chemosensitivity through the Nrf2-Mediated Pathway
title_fullStr	Luteolin Inhibits Breast Cancer Stemness and Enhances Chemosensitivity through the Nrf2-Mediated Pathway
title_full_unstemmed	Luteolin Inhibits Breast Cancer Stemness and Enhances Chemosensitivity through the Nrf2-Mediated Pathway
title_sort	luteolin inhibits breast cancer stemness and enhances chemosensitivity through the nrf2-mediated pathway
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/2613cc7450ad4f43a9ab4a40100bedae
work_keys_str_mv	AT kuenjangtsai luteolininhibitsbreastcancerstemnessandenhanceschemosensitivitythroughthenrf2mediatedpathway AT hsinyitsai luteolininhibitsbreastcancerstemnessandenhanceschemosensitivitythroughthenrf2mediatedpathway AT chinchuantsai luteolininhibitsbreastcancerstemnessandenhanceschemosensitivitythroughthenrf2mediatedpathway AT taiyuchen luteolininhibitsbreastcancerstemnessandenhanceschemosensitivitythroughthenrf2mediatedpathway AT tsunghuahsieh luteolininhibitsbreastcancerstemnessandenhanceschemosensitivitythroughthenrf2mediatedpathway AT chunlinchen luteolininhibitsbreastcancerstemnessandenhanceschemosensitivitythroughthenrf2mediatedpathway AT lulekiwembuyisa luteolininhibitsbreastcancerstemnessandenhanceschemosensitivitythroughthenrf2mediatedpathway AT yawbinhuang luteolininhibitsbreastcancerstemnessandenhanceschemosensitivitythroughthenrf2mediatedpathway AT mingweilin luteolininhibitsbreastcancerstemnessandenhanceschemosensitivitythroughthenrf2mediatedpathway
_version_	1718431812388126720

Luteolin Inhibits Breast Cancer Stemness and Enhances Chemosensitivity through the Nrf2-Mediated Pathway

Ejemplares similares