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

Scientific Reports
Wanjun LinWenzhe Ma

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 TNB...Continue Reading

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Citations

Aug 22, 2018·Oncology Letters·Magdalena CiążyńskaAleksandra Lesiak
Jan 16, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Win Sen Heng, Shiau-Chuen Cheah
Feb 14, 2021·Cell Biochemistry and Biophysics·Ling PengChangming Wang
Apr 8, 2021·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Jingjing DuWenzhe Ma

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Methods Mentioned

BETA
flow cytometry
Fluorescence
transfection
PCR
xenograt
xenograft

Software Mentioned

Prism
GENE
Compusyn
FlowJo

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