α-Pinene ức chế sự xâm lấn của khối u thông qua việc giảm điều hòa biểu hiện gen matrix metalloproteinase-9 do yếu tố hạt nhân (NF)-κB ở tế bào ung thư vú người MDA-MB-231

Eunah Kang1, Da Hyun Lee1, You Jung Jung2, Soon Young Shin1,2, Dongsoo Koh3, Young Han Lee1,2
1Department of Biological Sciences, College of Biological Science and Biotechnology, Konkuk University, Seoul, Republic of Korea
2Cancer and Metabolism Institute, Konkuk University, Seoul, Republic of Korea
3Department of Applied Chemistry, Dongduk Women’s University, Seoul, Republic of Korea

Tóm tắt

2,6,6-Trimethylbicyclo[3.1.1]hept-2-ene (α-Pinene) là một hợp chất hữu cơ thuộc nhóm terpen có trong tinh dầu của nhiều loại thực vật. Trong nghiên cứu này, tác động ức chế của α-pinene đối với sự xâm lấn khối u ở tế bào ung thư vú người MDA-MB-231 có khả năng di căn cao được đánh giá. α-Pinene đã ức chế tính xâm lấn của tế bào MDA-MB-231 được kích thích bởi yếu tố hoại tử khối u (TNF)-α như được tiết lộ bởi thử nghiệm xâm lấn hình cầu ba chiều. Phân tích thêm cho thấy α-pinene làm giảm hoạt động của promoter gen matrix metalloproteinase-9 và biểu hiện mRNA kích thích bởi TNFα theo tỷ lệ liều. Ngoài ra, điều trị bằng α-pinene đã làm giảm sự kích hoạt yếu tố hạt nhân κB (NF-κB) do TNFα và hoạt động phiên mã phụ thuộc NF-κB. Những kết quả này gợi ý rằng α-pinene có tác động đáng kể đến việc ức chế sự xâm lấn của khối u và có thể có tiềm năng được phát triển thành một loại thuốc chống di căn.

Từ khóa

#α-Pinene #MDA-MB-231 #sự xâm lấn khối u #yếu tố hoại tử khối u (TNF)-α #yếu tố hạt nhân κB (NF-κB)

Tài liệu tham khảo

Balkwill F (2009) Tumour necrosis factor and cancer. Nat Rev Cancer 9:361–371

Balkwill FR, Capasso M, Hagemann T (2012) The tumor microenvironment at a glance. J Cell Sci 125:5591–5596

Barnes PJ, Karin M (1997) Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 336:1066–1071

Chen W, Liu Y, Li M, Mao J, Zhang L, Huang R, Jin X, Ye L (2015) Anti-tumor effect of alpha-pinene on human hepatoma cell lines through inducing G2/M cell cycle arrest. J Pharmacol Sci 127:332–338

da Silva AC, Lopes PM, de Azevedo MM, Costa DC, Alviano CS, Alviano DS (2012) Biological activities of alpha-pinene and beta-pinene enantiomers. Molecules 17:6305–6316

Deryugina EI, Quigley JP (2006) Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev 25:9–34

Downes CP, Carter AN (1991) Phosphoinositide 3-kinase: a new effector in signal transduction? Cell Signal 3:501–513

Friedl P, Alexander S (2011) Cancer invasion and the microenvironment: plasticity and reciprocity. Cell 147:992–1009

Han YP, Tuan TL, Hughes M, Wu H, Garner WL (2001) Transforming growth factor-beta-and tumor necrosis factor-alpha-mediated induction and proteolytic activation of MMP-9 in human skin. J Biol Chem 276:22341–22350

Jing H, Zhou X, Dong X, Cao J, Zhu H, Lou J, Hu Y, He Q, Yang B (2010) Abrogation of Akt signaling by Isobavachalcone contributes to its anti-proliferative effects towards human cancer cells. Cancer Lett 294:167–177

Joyce JA, Pollard JW (2009) Microenvironmental regulation of metastasis. Nat Rev Cancer 9:239–252

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 44:369–377

Lee MS, Koh D, Kim GS, Lee SE, Noh HJ, Kim SY, Lee YH, Lim Y, Shin SY (2015) 2-Hydroxy-3,4-naphthochalcone (2H-NC) inhibits TNFalpha-induced tumor invasion through the downregulation of NF-kappaB-mediated MMP-9 gene expression. Bioorg Med Chem Lett 25:128–132

Lin CC, Tseng HW, Hsieh HL, Lee CW, Wu CY, Cheng CY, Yang CM (2008) Tumor necrosis factor-[alpha] induces MMP-9 expression via p42/p44 MAPK, JNK, and nuclear factor-[kappa]B in A549 cells. Toxicol Appl Pharmacol 229:386–398

Madrid LV, Wang CY, Guttridge DC, Schottelius AJ, Baldwin AS Jr, Mayo MW (2000) Akt suppresses apoptosis by stimulating the transactivation potential of the RelA/p65 subunit of NF-kappaB. Mol Cell Biol 20:1626–1638

Madrid LV, Mayo MW, Reuther JY, Baldwin AS Jr (2001) Akt stimulates the transactivation potential of the RelA/p65 Subunit of NF-kappa B through utilization of the Ikappa B kinase and activation of the mitogen-activated protein kinase p38. J Biol Chem 276:18934–18940

Mercier B, Prost J, Prost M (2009) The essential oil of turpentine and its major volatile fraction (alpha- and beta-pinenes): a review. Int J Occup Med Environ Health 22:331–342

Ozes ON, Mayo LD, Gustin JA, Pfeffer SR, Pfeffer LM, Donner DB (1999) NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine kinase. Nature 401:82–85

Pikarsky E, Porat RM, Stein I, Abramovitch R, Amit S, Kasem S, Gutkovich-Pyest E, Urieli-Shoval S, Galun E, Ben-Neriah Y (2004) NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature 431:461–466

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 14:291–300

Sarbassov DD, Guertin DA, Ali SM, Sabatini DM (2005) Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307:1098–1101

Shin SY, Kim JH, Baker A, Lim Y, Lee YH (2010) Transcription factor Egr-1 is essential for maximal matrix metalloproteinase-9 transcription by tumor necrosis factor alpha. Mol Cancer Res 8:507–519

Shin SY, Kim JH, Yoon H, Choi YK, Koh D, Lim Y, Lee YH (2013a) Novel antimitotic activity of 2-hydroxy-4-methoxy-2′,3′-benzochalcone (HymnPro) through the inhibition of tubulin polymerization. J Agric Food Chem 61:12588–12597

Shin SY, Lee JM, Lim Y, Lee YH (2013b) Transcriptional regulation of the growth-regulated oncogene alpha gene by early growth response protein-1 in response to tumor necrosis factor alpha stimulation. Biochim Biophys Acta 1829:1066–1074

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 49:4615–4621

Van den Steen PE, Dubois B, Nelissen I, Rudd PM, Dwek RA, Opdenakker G (2002) Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9). Crit Rev Biochem Mol Biol 37:375–536