Protein kinase C inhibitor chelerythrine selectively inhibits proliferation of triple-negative breast cancer cells

Abstract Triple-negative breast cancer (TNBC) is a subtype of breast cancer lacking targeted therapy currently. Recent studies imply that protein kinase C may play important roles in TNBC development and could be a specific target. In this study, we evaluated the anti-proliferative activity of PKC i...

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Autores principales:	Wanjun Lin, Jiajun Huang, Zhongwen Yuan, Senling Feng, Ying Xie, Wenzhe Ma
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/30a9236ffdf242609ca8aa3c42f629d8
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spelling	oai:doaj.org-article:30a9236ffdf242609ca8aa3c42f629d82021-12-02T12:32:20ZProtein kinase C inhibitor chelerythrine selectively inhibits proliferation of triple-negative breast cancer cells10.1038/s41598-017-02222-02045-2322https://doaj.org/article/30a9236ffdf242609ca8aa3c42f629d82017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02222-0https://doaj.org/toc/2045-2322Abstract Triple-negative breast cancer (TNBC) is a subtype of breast cancer lacking targeted therapy currently. Recent studies imply that protein kinase C may play important roles in TNBC development and could be a specific target. In this study, we evaluated the anti-proliferative activity of PKC inhibitor chelerythrine on a panel of breast cancer cell lines. Chelerythrine selectively inhibited the growth of TNBC cell lines compared to non-TNBC cell lines as demonstrated by in vitro cell proliferation assay and colony formation assay, as well as evidenced by in vivo xenograft assay. The selective anti-proliferative effect of chelerythrine was associated with induction of apoptosis in TNBC cell lines. We further demonstrated that PKN2, one of the PKC subtypes, was highly expressed in TNBC cell lines, and knocking down PKN2 in TNBC cells inhibited colony formation and xenograft growth. This indicates that PKN2 is required for the survival of TNBC cells, and could be the target mediates the selective activity of chelerythrine. Finally, combination of chelerythrine and chemotherapy reagent taxol showed synergistic/additive effect on TNBC cell lines. Our results suggest chelerythrine or other PKC inhibitors may be promising regimens for TNBC tumors.Wanjun LinJiajun HuangZhongwen YuanSenling FengYing XieWenzhe MaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wanjun Lin Jiajun Huang Zhongwen Yuan Senling Feng Ying Xie Wenzhe Ma Protein kinase C inhibitor chelerythrine selectively inhibits proliferation of triple-negative breast cancer cells
description	Abstract Triple-negative breast cancer (TNBC) is a subtype of breast cancer lacking targeted therapy currently. Recent studies imply that protein kinase C may play important roles in TNBC development and could be a specific target. In this study, we evaluated the anti-proliferative activity of PKC inhibitor chelerythrine on a panel of breast cancer cell lines. Chelerythrine selectively inhibited the growth of TNBC cell lines compared to non-TNBC cell lines as demonstrated by in vitro cell proliferation assay and colony formation assay, as well as evidenced by in vivo xenograft assay. The selective anti-proliferative effect of chelerythrine was associated with induction of apoptosis in TNBC cell lines. We further demonstrated that PKN2, one of the PKC subtypes, was highly expressed in TNBC cell lines, and knocking down PKN2 in TNBC cells inhibited colony formation and xenograft growth. This indicates that PKN2 is required for the survival of TNBC cells, and could be the target mediates the selective activity of chelerythrine. Finally, combination of chelerythrine and chemotherapy reagent taxol showed synergistic/additive effect on TNBC cell lines. Our results suggest chelerythrine or other PKC inhibitors may be promising regimens for TNBC tumors.
format	article
author	Wanjun Lin Jiajun Huang Zhongwen Yuan Senling Feng Ying Xie Wenzhe Ma
author_facet	Wanjun Lin Jiajun Huang Zhongwen Yuan Senling Feng Ying Xie Wenzhe Ma
author_sort	Wanjun Lin
title	Protein kinase C inhibitor chelerythrine selectively inhibits proliferation of triple-negative breast cancer cells
title_short	Protein kinase C inhibitor chelerythrine selectively inhibits proliferation of triple-negative breast cancer cells
title_full	Protein kinase C inhibitor chelerythrine selectively inhibits proliferation of triple-negative breast cancer cells
title_fullStr	Protein kinase C inhibitor chelerythrine selectively inhibits proliferation of triple-negative breast cancer cells
title_full_unstemmed	Protein kinase C inhibitor chelerythrine selectively inhibits proliferation of triple-negative breast cancer cells
title_sort	protein kinase c inhibitor chelerythrine selectively inhibits proliferation of triple-negative breast cancer cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/30a9236ffdf242609ca8aa3c42f629d8
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Protein kinase C inhibitor chelerythrine selectively inhibits proliferation of triple-negative breast cancer cells

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