Tectorigenin ablates the inflammation-induced epithelial–mesenchymal transition in a co-culture model of human lung carcinoma
Tóm tắt
Tumors not only manage to escape from the host immune system, but they effectively contrive to benefit from infiltrating immune cells by modifying their functions so as to create a pro-inflammatory microenvironment favorable for tumor progression and metastasis. In this study we investigated if tectorigenin could suppress lung cancer-induced pro-inflammatory response generated from monocytes. A549:THP1 co-culture model was set-up favoring release of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α). Effect of tectorigenin on A549 imparted invasive phenotype of A549:THP-1 co-culture was monitored by cytokine release from monocytes, and metastasis/epithelial–mesenchymal transitiom (EMT) in A549 cells. In a contact A549:THP1 co-culture model, THP-1 cells were activated by A549 cells favoring secretion of pro-inflammatory cytokines, TNF-α and IL-6. However, priming of A549 cells with tectorigenin for 24 h repressed A549 cell-induced secretion of TNF-α and IL-6 by THP-1 cells. Tectorigenin induced change in functional phenotype of A549 cells rendered THP-1 cells non-responsive for the secretion of IL-6 and TNF-α in a contact co-culture setup. Additionally, conditioned media from this non-responsive A549:THP-1 co-culture suppressed metastatic potential of A549 cells as confirmed by the wound healing and transwell migration assays. These finding were further corroborated by decrease in expression of Snail with a concomitant increase in E-cadherin, the two signature markers of EMT. These results clearly demonstrate the therapeutic potential of tectorigenin to prevent lung cancer elicited inflammatory and pro-metastatic response in monocytes and warrants further investigations to elucidate its mechanism of action.
Tài liệu tham khảo
Kim S, Takahashi H, Lin WW, Descargues P, Grivennikov S, Kim Y, et al. Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis. Nature 2009;457:102–6.
DeNardo DG, Andreu P, Coussens LM. Interactions between lymphocytes and myeloid cells regulate pro- versus anti-tumor immunity. Cancer Metastasis Rev 2010;29:309–16.
Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell 2010;141:39–51.
Thiery JP, Chua K, Sim WJ, Huang R. Epithelial to mesenchymal transition during development in fibrosis and in the progression of carcinoma. Bull Cancer 2010;97:1285–95.
Comijn J, Berx G, Vermassen P, Verschueren K, van Grunsven L, Bruyneel E, et al. The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Mol Cell 2001;7:1267–78.
Hajra KM, Chen DY, Fearon ER. The SLUG zinc-finger protein represses E-cadherin in breast cancer. Cancer Res 2002;62:1613–8.
Bolos V, Peinado H, Perez-Moreno MA, Fraga MF, Esteller M, Cano A. The transcription factor slug represses E-cadherin expression and induces epithelial to mesenchymal transitions: a comparison with Snail and E47 repressors. J Cell Sci 2003;116:499–511.
Batlle E, Sancho E, Franci C, Dominguez D, Monfar M, Baulida J, et al. The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol 2000;2:84–9.
Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, et al. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 2004;117:927–39.
Hartwell KA, Muir B, Reinhardt F, Carpenter AE, Sgroi DC, Weinberg RA. The Spemann organizer gene, Goosecoid, promotes tumor metastasis. Proc Natl Acad Sci U S A 2006;103:18969–74.
Eger A, Aigner K, Sonderegger S, Dampier B, Oehler S, Schreiber M, et al. Delta EF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells. Oncogene 2005;24:2375–85.
Perez-Moreno MA, Locascio A, Rodrigo I, Dhondt G, Portillo F, Nieto MA, et al. A new role for E12/E47 in the repression of E-cadherin expression and epithelial–mesenchymal transitions. J Biol Chem 2001;276:27424–31.
Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial–mesenchymal transitions in development and disease. Cell 2009;139:871–90.
Kalluri R, Weinberg RA. The basics of epithelial–mesenchymal transition. J Clin Invest 2009;119:1420–8.
Huber MA, Kraut N, Beug H. Molecular requirements for epithelial–mesenchymal transition during tumor progression. Curr Opin Cell Biol 2005;17:548–58.
Miyamoto S, Nishiumi S, Kawabata K, Ohnishi K, Mukai R, Ashida H, et al. Dietary flavonoids as cancer-preventive and therapeutic biofactors. Front Biosci (Schol Ed) 2011;3:1332–62.
Shin JE, Bae EA, Lee YC, Ma JY, Kim DH. Estrogenic effect of main components kakkalide and tectoridin of Puerariae Flos and their metabolites. Biol Pharm Bull 2006;29:1202–6.
Pan CH, Kim ES, Jung SH, Nho CW, Lee JK. Tectorigenin inhibits IFN-gamma/LPS-induced inflammatory responses in murine macrophage RAW 264.7 cells. Arch Pharm Res 2008;31:1447–56.
Yang YI, Lee KT, Park HJ, Kim TJ, Choi YS, Shih IM, et al. Tectorigenin sensitizes paclitaxel-resistant human ovarian cancer cells through downregulation of the Akt and NFκB pathway. Carcinogenesis 2012;33:2488–98.
Wani SH, Amin A, Sofi SN, Mokhdomi TA, Bukhari S, Hassan QP, et al. RP-HPLC facilitated quantitative analysis of tectorigenin in the different species of Iris plant and evaluation of its in vitro anticancer potential. Int J Curr Res 2013;5:206–11.
Kim YP, Yamada M, Lim SS, Lee SH, Ryu N, Shin KH, et al. Inhibition by tectorigenin and tectoridin of prostaglandin E2 production and cyclooxygenase-2 induction in rat peritoneal macrophages. Biochim Biophys Acta 1999;1438:399–407.
Kim HK, Cheon BS, Kim YH, Kim SY, Kim HP. Effects of naturally occurring flavonoids on nitric oxide production in the macrophage cell line RAW 264.7 and their structure–activity relationships. Biochem Pharmacol 1999;58:759–65.
Rah B, Amin H, Yousuf K, Khan S, Jamwal G, Mukherjee D, et al. A novel MMP-2 inhibitor 3-azidowithaferin A (3-azidoWA) abrogates cancer cell invasion and angiogenesis by modulating extracellular par-4. PLoS ONE 2012;7:e44039.
Wu Y, Deng J, Rychahou PG, Qiu S, Evers BM, Zhou BP. Stabilization of Snail by NF-κB is required for inflammation-induced cell migration and invasion cancer. Cell 2009;15:416–28.
Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature 2008;454:436–44.
Mantovani A, Sica A. Macrophages, innate immunity and cancer: balance, tolerance, and diversity. Curr Opin Immunol 2010;22:231–7.
Torisu H, Ono M, Kiryu H, Furue M, Ohmoto Y, Nakayama J, et al. Macrophage infiltration correlates with tumor stage and angiogenesis in human malignant melanoma: possible involvement of TNFα and IL-1α. Int J Cancer 2000;85:182–8.
Rayburn R, Scharri JE, Zhang R. Anti-inflammatory agents for cancer therapy. Mol Cell Pharmacol 2009;1:29–43.
Ricchi P, Zarrilli R, Di Palma A, Acquaviva AM. Anti-inflammatory drugs in colorectal cancer: from prevention to therapy. Br J Cancer 2003;88: 803–7.
Ha LM, Que DTN, Huyen DTT, Long PQ, Dat NT. Toxicity, analgesic and anti-inflammatory activities of tectorigenin. Immunopharmacol Immunotoxicol 2013;35(3):336–40.
Thiery JP. Epithelial–mesenchymal transitions in tumour progression. Nat Rev Cancer 2002;2:442–54.
Wu Y, Deng J, Rychahou PG, Qiu S, Evers BM, Zhou BP. Stabilization of Snail by NF-κB is required for inflammation-induced cell migration and invasion. Cancer Cell 2009;15:416–28.