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

• Published in: Scientific reports Vol. 7; no. 1; pp. 2022 - 12
• Main Authors: Lin, Wanjun, Huang, Jiajun, Yuan, Zhongwen, Feng, Senling, Xie, Ying, Ma, Wenzhe
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.05.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 13/2; 13/31; 38/61; 38/90; 45; 45/77; 692/4017; 692/4028/67/1347; 96/63; Animals; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Benzophenanthridines - pharmacology; Breast cancer; Cell Cycle - drug effects; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Chelerythrine; Chemotherapy; Colonies; Disease Models, Animal; Enzyme inhibitors; Female; Gene Expression Regulation, Neoplastic - drug effects; Gene Knockdown Techniques; Humanities and Social Sciences; Humans; Isoenzymes - antagonists & inhibitors; Kinases; Mice; multidisciplinary; Paclitaxel; Paclitaxel - pharmacology; Protein kinase C; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - genetics; Protein Kinase C - metabolism; Protein Kinase Inhibitors - pharmacology; Science; Science (multidisciplinary); Triple Negative Breast Neoplasms - genetics; Triple Negative Breast Neoplasms - metabolism; Tumor cell lines; Tumors; Xenograft Model Antitumor Assays; Xenografts
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-02222-0

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.