The induction of activating transcription factor 3 (ATF3) contributes to anti-cancer activity of Abeliophyllum distichum Nakai in human colorectal cancer cells

BMC Complementary and Alternative Medicine

Jin Boo Jeong⁴  Jin Suk Koo¹  Jeong Rak Lee²  Man Hyo Lee²  Jin Wook Lee⁵  Mi Kyoung Kim⁵  So Hee Woo⁵  Hun Min Song⁵  Hyun Ji Eo⁵  Jae Ho Park³  Gwang Hun Park⁵ 

[1] Insititute of Agricultural Science and Technology, Andong National University, Andong 760749, Korea;Gyeongbuk Institute for Bio-industry, Andong 760380, Korea;Department of Medicinal Plant Science, Jungwon University, Goesan 367805, Korea;Department of Medicinal Plant Resources, Andong National University, Andong 760749, Korea;Department of Bioresource Sciences, Andong National University, Andong 760749, Korea

关键词: Colorectal cancer;    Cancer chemoprevention;    Apoptosis;    Activating transcription factor 3;    Abeliophyllum distichum Nakai;   

Others  :  1084895
DOI  :  10.1186/1472-6882-14-487

 received in 2014-04-29, accepted in 2014-12-11,  发布年份 2014

【 摘 要 】

Background

Recently, Abeliophyllum distichum Nakai (A. distichum) has been reported to exert the inhibitory effect on angiotensin converting enzyme. However, no specific pharmacological effects from A. distichum have been described. We performed in vitro study to evaluate anti-cancer properties of A. distichum and then elucidate the potential mechanisms.

Methods

Cell viability was measured by MTT assay. ATF3 expression level was evaluated by Western blot or RT-PCR and ATF3 transcriptional activity was determined using a dual-luciferase assay kit after the transfection of ATF3 promoter constructs. In addition, ATF3-dependent apoptosis was evaluated by Western blot after ATF3 knockdown using ATF3 siRNA.

Results

Exposure of ethyl acetate fraction from the parts of A. distichum including flower, leaf and branch to human colorectal cancer cells, breast cancer cells and hepatocellular carcinoma reduced the cell viability. The branch extracts from A. distichum (EAFAD-B) increased the expression of activating transcription factor 3 (ATF3) and promoter activity, indicating transcriptional activation of ATF3 gene by EAFAD-B. In addition, our data showed that EAFAD-B-responsible sites might be between -147 and -85 region of the ATF3 promoter. EAFAD-B-induced ATF3 promoter activity was significantly decreased when the CREB site was deleted. However, the deletion of Ftz sites did not affect ATF3 promoter activity by EAFAD-B. We also observed that inhibition of p38MAPK and GSK3β attenuated EAFAD-B-mediated ATF3 promoter activation. Also, EAFAD-B contributes at least in part to increase of ATF3 accumulation.

Conclusion

These findings suggest that the anti-cancer activity of EAFAD-B may be a result of ATF3 promoter activation and subsequent increase of ATF3 expression.

【 授权许可】

   
2014 Park et al.; licensee BioMed Central.

【 图 表 】

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【 参考文献 】

• [1]Oh H, Kang DG, Kwon TO, Jang KK, Chai KY, Yun YG, Chung HT, Lee HS: Four glycosides from the leaves of Abeliophyllum distichum with inhibitory effects on angiotensin converting enzyme. Phytother Res 2003, 17(7):811-813.
• [2]Hai T, Hartman MG: The molecular biology and nomenclature of the activating transcription factor/cAMP responsive element binding family of transcription factors: activating transcription factor proteins and homeostasis. Gene 2001, 273(1):1-11.
• [3]Cai Y, Zhang C, Nawa T, Aso T, Tanaka M, Oshiro S, Ichijo H, Kitajima S: Homocysteine-responsive ATF3 gene expression in human vascular endothelial cells: activation of c-Jun NH(2)-terminal kinase and promoter response element. Blood 2000, 96(6):2140-2148.
• [4]Yin T, Sandhu G, Wolfgang CD, Burrier A, Webb RL, Rigel DF, Hai T, Whelan J: Tissue-specific pattern of stress kinase activation in ischemic/reperfused heart and kidney. J Biol Chem 1997, 272(32):19943-19950.
• [5]Iyer VR, Eisen MB, Ross DT, Schuler G, Moore T, Lee JC, Trent JM, Staudt LM, Hudson J Jr, Boguski MS, Lashkari D, Shalon D, Botstein D, Brown PO: The transcriptional program in the response of human fibroblasts to serum. Science 1999, 283(5398):83-87.
• [6]Allan AL, Albanese C, Pestell RG, LaMarre J: Activating transcription factor 3 induces DNA synthesis and expression of cyclin D1 in hepatocytes. J Biol Chem 2001, 276(29):27272-27280.
• [7]Yan L, Della Coletta L, Powell KL, Shen J, Thames H, Aldaz CM, MacLeod MC: Activation of the canonical Wnt/beta-catenin pathway in ATF3-induced mammary tumors. PLoS One 2011, 6(1):e16515.
• [8]Yamaguchi K, Lee SH, Kim JS, Wimalasena J, Kitajima S, Baek SJ: Activating transcription factor 3 and early growth response 1 are the novel targets of LY294002 in a phosphatidylinositol 3-kinase-independent pathway. Cancer Res 2006, 66(4):2376-2384.
• [9]Cho KN, Sukhthankar M, Lee SH, Yoon JH, Baek SJ: Green tea catechin (-)-epicatechin gallate induces tumour suppressor protein ATF3 via EGR-1 activation. Eur J Cancer 2007, 43(16):2404-2412.
• [10]Lee SH, Min KW, Zhang X, Baek SJ: 3,3'-diindolylmethane induces activating transcription factor 3 (ATF3) via ATF4 in human colorectal cancer cells. J Nutr Biochem 2013, 24(4):664-671.
• [11]St Germain C, Niknejad N, Ma L, Garbuio K, Hai T, Dimitroulakos J: Cisplatin induces cytotoxicity through the mitogen-activated protein kinase pathways and activating transcription factor 3. Neoplasia 2010, 12(7):527-538.
• [12]Bruning A, Burger P, Vogel M, Rahmeh M, Friese K, Lenhard M, Burges A: Bortezomib treatment of ovarian cancer cells mediates endoplasmic reticulum stress, cell cycle arrest, and apoptosis. Investig New Drugs 2009, 27(6):543-551.
• [13]Lee SH, Kim JS, Yamaguchi K, Eling TE, Baek SJ: Indole-3-carbinol and 3,3'-diindolylmethane induce expression of NAG-1 in a p53-independent manner. Biochem Biophys Res Commun 2005, 328(1):63-69.
• [14]Lee SH, Yamaguchi K, Kim JS, Eling TE, Safe S, Park Y, Baek SJ: Conjugated linoleic acid stimulates an anti-tumorigenic protein NAG-1 in an isomer specific manner. Carcinogenesis 2006, 27(5):972-981.
• [15]Baek SJ, Kim JS, Jackson FR, Eling TE, McEntee MF, Lee SH: Epicatechin gallate-induced expression of NAG-1 is associated with growth inhibition and apoptosis in colon cancer cells. Carcinogenesis 2004, 25(12):2425-2432.
• [16]Yin X, Dewille JW, Hai T: A potential dichotomous role of ATF3, an adaptive-response gene, in cancer development. Oncogene 2008, 27(15):2118-2127.
• [17]Dong Y, Asch HL, Ying A, Asch BB: Molecular mechanism of transcriptional repression of gelsolin in human breast cancer cells. Exp Cell Res 2002, 276(2):328-336.
• [18]Niknejad N, Gorn-Hondermann I, Ma L, Zahr S, Johnson-Obeseki S, Corsten M, Dimitroulakos J: Lovastatin-induced apoptosis is mediated by activating transcription factor 3 and enhanced in combination with salubrinal. Int J Cancer 2014, 134(2):268-279.
• [19]Colin-Cassin C, Yao X, Cerella C, Chbicheb S, Kuntz S, Mazerbourg S, Boisbrun M, Chapleur Y, Diederich M, Flament S, Grillier-Vuissoz I: PPARgamma-inactive Delta2-troglitazone independently triggers ER stress and apoptosis in breast cancer cells. Mol Carcinog 2013. doi:10.1002/mc.22109. [Epub ahead of print]
• [20]Lee YM, Uhm KO, Lee ES, Kwon J, Park SH, Kim HS: AM251 suppresses the viability of HepG2 cells through the AMPK (AMP-activated protein kinase)-JNK (c-Jun N-terminal kinase)-ATF3 (activating transcription factor 3) pathway. Biochem Biophys Res Commun 2008, 370(4):641-645.
• [21]Hai T, Wolfgang CD, Marsee DK, Allen AE, Sivaprasad U: ATF3 and stress responses. Gene Expr 1999, 7(4–6):321-335.
• [22]Mo P, Wang H, Lu H, Boyd DD, Yan C: MDM2 mediates ubiquitination and degradation of activating transcription factor 3. J Biol Chem 2010, 285(35):26908-26915.
• [23]Liang G, Wolfgang CD, Chen BP, Chen TH, Hai T: ATF3 gene. Genomic organization, promoter, and regulation. J Biol Chem 1996, 271(3):1695-1701.
• [24]Fu L, Kilberg MS: Elevated cJUN expression and an ATF/CRE site within the ATF3 promoter contribute to activation of ATF3 transcription by the amino acid response. Physiol Genomics 2013, 45(4):127-137.
• [25]Lee SH, Bahn JH, Whitlock NC, Baek SJ: Activating transcription factor 2 (ATF2) controls tolfenamic acid-induced ATF3 expression via MAP kinase pathways. Oncogene 2010, 29(37):5182-5192.