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KMID : 1094720220270060995
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Biotechnology and Bioprocess Engineering
2022 Volume.27 No. 6 p.995 ~ p.1003
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Ginkgolide B Suppresses TPA-induced Metastatic Potential in MCF-7 Human Breast Cancer Cells by Inhibiting MAPK/AP-1 Signaling
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Lee Min-Gu
Lee Sang-Gil
Nam Kyung-Soo
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Abstract
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Ginkgolide B (GKB) is a natural terpenoid lactone found in leaves of Ginkgo biloba and has antioxidative, anti-inflammatory, and anti-tumor activities. Here, we assessed the inhibitory effect of GKB on the 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced metastatic potential in MCF-7 cells (a human hormone receptor-positive breast cancer cell line). Gelatin zymography showed that GKB inhibited TPA-induced matrix metalloprotease-9 (MMP-9) activity, and wound healing and Matrigel invasion assays showed GKB inhibited TPA-induced cell migration and invasiveness. Furthermore, GKB suppressed the TPA-induced mRNA expressions of epithelial to mesenchymal transition (EMT) markers Slug, Snail, and Fibronectin genes. Based on these results, we assessed the effects of GKB on the phosphorylation of mitogen-activated protein kinases (MAPKs) and the expressions of c-Jun and c-Fos (two subunits of activating protein-1 [AP-1] and key regulators of the expressions of metastatic factors). GKB inhibited the phosphorylations of p38 (p38 mitogen-activated protein kinases) and JNK (c-Jun N-terminal kinase) and the expressions and nuclear translocations of c-Jun and c-Fos. These results demonstrate that the anti-metastatic effect of GKB is mediated by MAPK/AP-1 pathways suppression and consequent inhibitions of the MMP-9 activities and mRNA levels of EMT markers in TPA-treated MCF-7 cells. Our results suggest that GKB might be able to suppress metastasis in hormone receptor-positive breast cancer.
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KEYWORD
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ginkgolide B, breast cancer, metastasis, matrix metalloproteinase-9, activator protein-1
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