α-Pinene inhibits tumor invasion through downregulation of nuclear factor (NF)-κB-regulated matrix metalloproteinase-9 gene expression in MDA-MB-231 human breast cancer cells
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2,6,6-Trimethylbicyclo[3.1.1]hept-2-ene (α-Pinene) is an organic compound of the terpene class found in the essential oil of many plants. In this study, the inhibitory effect of α-pinene on tumor invasion in highly metastatic MDA-MB-231 human breast cancer cells was evaluated. α-Pinene inhibited tumor necrosis factor (TNF)-α-induced invasiveness of MDA-MB-231 cells as revealed by three-dimensional spheroid invasion assay. Further analysis showed that α-pinene reduced TNFα-induced matrix metalloproteinase-9 gene promoter activation and mRNA expression in a dose-dependent manner. In addition, α-pinene treatment attenuated TNFα-induced nuclear factor κB (NF-κB) activation and NF-κB-dependent transcriptional activity. These results suggest that α-pinene has a significant effect on the inhibition of tumor invasion and may potentially be developed into an anti-metastatic drug.
Keywords2,6,6-Trimethylbicyclo[3.1.1]hept-2-ene Breast cancer Matrix metalloproteinase-9 Nuclear factor kappa B Tumor invasion Tumor necrosis factor alpha
This study was supported by the Konkuk University research support program.
- Lee YH, Jeon SH, Kim SH, Kim C, Lee SJ, Koh D, Lim Y, Ha K, Shin SY (2012) A new synthetic chalcone derivative, 2-hydroxy-3′,5,5′-trimethoxychalcone (DK-139), suppresses the Toll-like receptor 4-mediated inflammatory response through inhibition of the Akt/NF-kappaB pathway in BV2 microglial cells. Exp Mol Med 44:369–377CrossRefGoogle Scholar
- Rao VH, Singh RK, Delimont DC, Finnell RH, Bridge JA, Neff JR, Garvin BP, Pickering DL, Sanger WG, Buehler BA, Schaefer GB (1999) Transcriptional regulation of MMP-9 expression in stromal cells of human giant cell tumor of bone by tumor necrosis factor-alpha. Int J Oncol 14:291–300Google Scholar
- Ura H, Bonfil RD, Reich R, Reddel R, Pfeifer A, Harris CC, Klein-Szanto AJ (1989) Expression of type IV collagenase and procollagen genes and its correlation with the tumorigenic, invasive, and metastatic abilities of oncogene-transformed human bronchial epithelial cells. Cancer Res 49:4615–4621Google Scholar