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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| Format: | Article |
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Nature Portfolio
2017-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-02222-0 |
| _version_ | 1818845631330910208 |
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| 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 |
| collection | DOAJ |
| 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. |
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| format | Article |
| id | doaj.art-30a9236ffdf242609ca8aa3c42f629d8 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T05:32:44Z |
| publishDate | 2017-05-01 |
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| series | Scientific Reports |
| spelling | doaj.art-30a9236ffdf242609ca8aa3c42f629d82022-12-21T20:34:11ZengNature PortfolioScientific Reports2045-23222017-05-017111210.1038/s41598-017-02222-0Protein kinase C inhibitor chelerythrine selectively inhibits proliferation of triple-negative breast cancer cellsWanjun Lin0Jiajun Huang1Zhongwen Yuan2Senling Feng3Ying Xie4Wenzhe Ma5State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and TechnologyState Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and TechnologyState Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and TechnologyState Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and TechnologyState Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and TechnologyState Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and TechnologyAbstract 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.https://doi.org/10.1038/s41598-017-02222-0 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-017-02222-0 |
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