Abstract
Metadherin (MTDH), a novel oncoprotein, has been implicated in the carcinogenesis in various aspects of tumor malignancy. Overexpression of the MTDH promotes the survival and proliferation of lung cancer cells. Agent that can suppress MTDH activation would have potential to be developed for cancer therapeutics. In this study, we investigated the antitumor effect of evodiamine in human non-small-cell lung carcinoma (NSCLC) A549 cell line and the inhibitory effect of evodiamine on MTDH pathway. 3-(4,5-Dimethyl- thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and annexin V/propidium iodide (PI) staining assays demonstrated that evodiamine or MTDH short hairpin RNA (shRNA) significantly inhibited proliferation of A549 cells via induction of apoptosis. Besides, evodiamine or MTDH shRNA-induced activation of the caspase-3 in A549 cells under same conditions. In addition, Western blotting analysis showed that treatment of A549 cells with evodiamine or MTDH shRNA resulted in an increase of proapoptotic protein Bax expression but decreased the expression levels of antiapoptotic protein Bcl-2 and MTDH, which altogether account for apoptotic cell death. Taken together, our results suggest that the evodiamine suppress the proliferation of lung cancer cells, at least, in part, via inhibition of MTDH expression and activation of apoptosis.
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References
Yamanaka R. Medical management of brain metastases from lung cancer (review). Oncol Rep. 2009;22:1269–76.
Jemal A, Siegel R, Ward E. Cancer statistics, 2007. CA Cancer J Clin. 2007;57:43–66.
Alberg AJ, Samet JM. Epidemiology of lung cancer. Chest. 2003;123(1 Suppl):21S–49S.
Zochbauer-Muller S, Gazdar AF, Minna JD. Molecular pathogenesis of lung cancer. Annu Rev Physiol. 2002;64:681–708.
Erridge SC, Møller H, Price A, Brewster D. International comparisons of survival from lung cancer: pitfalls and warnings. Nat Clin Pract Oncol. 2007;4:570–7.
Park KI, Park HS, Kang SR, Nagappan A, Lee DH, Kim JA, et al. Korean Scutellaria baicalensis water extract inhibits cell cycle G1/S transition by suppressing cyclin D1 expression and matrix-metalloproteinase-2 activity in human lung cancer cells. J Ethnopharmacol. 2011;133:634–41.
Murer B. Targeted therapy in non-small cell lung cancer: a commentary. Arch Pathol Lab Med. 2008;132:1573–5.
Kan SF, Yu CH, Pu HF, Hsu JM, Chen MJ, Wang PS. Anti-proliferative effects of evodiamine on human prostate cancer cell lines DU145 and PC3. J Cell Biochem. 2007;101:44–56.
Jiang J, Hu C. Evodiamine: a novel anti-cancer alkaloid from Evodia rutaecarpa. Molecules. 2009;14:1852–9.
Yu H, Jin H, Gong W, Wang Z, Liang H. Pharmacological actions of multi-target-directed evodiamine. Molecules. 2013;18:1826–43.
Shin YW, Bae EA, Cai XF, Lee JJ, Kim DH. In vitro and in vivo antiallergic effect of the fructus of Evodia rutaecarpa and its constituents. Biol Pharm Bull. 2007;30:197–9.
Chiou WF, Sung YJ, Liao JF, Shum AY, Chen CF. Inhibitory effect of dehydroevodiamine and evodiamine on nitric oxide production in cultured murine macrophages. J Nat Prod. 1997;60:708–11.
Kobayashi Y, Nakano Y, Kizaki M, Hoshikuma K, Yokoo Y, Kamiya T. Capsaicin-like anti-obese activities of evodiamine from fruits of Evodia rutaecarpa, a vanilloid receptor agonist. Planta Med. 2001;67:628–33.
Kobayashi Y. The nociceptive and anti-nociceptive effects of evodiamine from fruits of Evodia rutaecarpa in mice. Planta Med. 2003;69:425–8.
Rang WQ, Du YH, Hu CP, Ye F, Xu KP, Peng J, et al. Protective effects of evodiamine on myocardial ischemia-reperfusion injury in rats. Planta Med. 2004;70:1140–3.
Lin H, Tsai SC, Chen JJ, Chiao YC, Wang SW, Wang GJ, et al. Effects of evodiamine on the secretion of testosterone in rat testicular interstitial cells. Metabolism. 1999;48:1532–5.
Fei XF, Wang BX, Li TJ, Tashiro S, Minami M, Xing DJ, et al. Evodiamine, a constituent of Evodiae Fructus, induces anti-proliferating effects in tumor cells. Cancer Sci. 2003;94:92–8.
Yang ZG, Chen AQ, Liu B. Antiproliferation and apoptosis induced by evodiamine in human colorectal carcinoma cells (COLO-205). Chem Biodivers. 2009;6:924–33.
Huang H, Zhang Y, Liu X, Li Z, Xu W, He S, et al. Acid sphingomyelinase contributes to evodiamine-induced apoptosis in human gastric cancer SGC-7901 cells. DNA Cell Biol. 2011;30:407–12.
Yang L, Liu X, Wu D, Zhang M, Ran G, Bi Y, et al. Growth inhibition and induction of apoptosis in SGC‑7901 human gastric cancer cells by evodiamine. Mol Med Rep. 2014;9:1147–52.
Yang J, Wu LJ, Tashino S, Onodera S, Ikejima T. Protein tyrosine kinase pathway-derived ROS/NO productions contribute to G2/M cell cycle arrest in evodiamine-treated human cervix carcinoma HeLa cells. Free Radic Res. 2010;44:792–802.
Zhu LH, Liu XD, Tan YH, Li JF, Du BY, Wu YY. Proliferation-inhibited and apoptosis-inducted effects of evodiamine on human hepatoma cell line HepG2. Chin Pharmacol Bull. 2009;25:79–82.
Kan SF, Huang WJ, Lin LC, Wang PS. Inhibitory effects of evodiamine on the growth of human prostate cancer cell line LNCaP. Int J Cancer. 2004;110:641–51.
Wang C, Li S, Wang MW. Evodiamine-induced human melanoma A375-S2 cell death was mediated by PI3K/Akt/caspase and Fas-L/NF-kappaB signaling pathways and augmented by ubiquitin-proteasome inhibition. Toxicol In Vitro. 2010;24:898–904.
Ogasawara M, Matsunaga T, Takahashi S, Saiki I, Suzuki H. Anti-invasive and metastatic activities of evodiamine. Biol Pharm Bull. 2002;25:1491–3.
Liao CH, Pan SL, Guh JH, Chang YL, Pai HC, Lin CH, et al. Antitumor mechanism of evodiamine, a constituent from Chinese herb Evodiae fructus, in human multiple-drug resistant breast cancer NCI/ADR-RES cells in vitro and in vivo. Carcinogenesis. 2005;26:968–75.
Yoo BK, Gredler R, Vozhilla N, Su ZZ, Chen D, Forcier T, et al. Identification of genes conferring resistance to 5-fluorouracil. Proc Natl Acad Sci U S A. 2009;106:12938–43.
Kock N, Kasmieh R, Weissleder R, Shah K. Tumor therapy mediated by lentiviral expression of shBcl-2 and S-TRAIL. Neoplasia. 2007;9:435–42.
Jiang S, Zu Y, Fu Y, Zhang Y, Efferth T. Activation of the mitochondria-driven pathway of apoptosis in human PC-3 prostate cancer cells by a novel hydrophilic paclitaxel derivative, 7-xylosyl-10-deacetylpaclitaxel. Int J Oncol. 2008;33:103–11.
Kawiak A, Zawacka-Pankau J, Lojkowska E. Plumbagin induces apoptosis in Her2-overexpressing breast cancer cells through the mitochondrial-mediated pathway. J Nat Prod. 2012;75:747–51.
Alosi JA, McDonald DE, Schneider JS, Privette AR, McFadden DW. Pterostilbene inhibits breast cancer in vitro through mitochondrial depolarization and induction of caspase-dependent apoptosis. J Surg Res. 2010;161:195–201.
Shang LH, Li CM, Yang ZY, Che DH, Cao JY, Yu Y. Luffa echinata Roxb. induces human colon cancer cell (HT-29) death by triggering the mitochondrial apoptosis pathway. Molecules. 2012;17:5780–94.
Rasul A, Yu B, Zhong L, Khan M, Yang H, Ma T. Cytotoxic effect of evodiamine in SGC-7901 human gastric adenocarcinoma cells via simultaneous induction of apoptosis and autophagy. Oncol Rep. 2012;27:1481–7.
Saraste A, Pulkki K. Morphologic and biochemical hallmarks of apoptosis. Cardiovasc Res. 2000;45:528–37.
Danial NN, Korsmeyer SJ. Cell death: Critical control points. Cell. 2004;116:205–19.
Ghavami S, Hashemi M, Ande SR, Yeganeh B, Xiao W, Eshraghi M, et al. Apoptosis and cancer: mutations within caspase genes. J Med Genet. 2009;46:497–510.
Lavrik IN, Golks A, Krammer PH. Caspases: pharmacological manipulation of cell death. J Clin Invest. 2005;115:2665–72.
Lazebnik YA, Kaufmann SH, Desnoyers S, Poirier GG, Earnshaw WC. Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE. Nature. 1994;371:346–7.
Tewari M, Quan LT, O'Rourke K, Desnoyers S, Zeng Z, Beidler DR, et al. Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase. Cell. 1995;81:801–9.
Orrenius S. Mitochondrial regulation of apoptotic cell death. Toxicol Lett. 2004;149:19–23.
van Laethem A, van Kelst S, Lippens S, Declercq W, Vandenabeele P, Janssens S, et al. Activation of p38MAPK is required for Bax translocation tomitochondria, cytochrome c release and apoptosis induced by UVB irradiation in human keratinocytes. FASEB J. 2004;18:1946–8.
Vander Heiden MG, Thompson CB. Bcl-2 protiens: regulators of apoptosis or of mitochondrial homeostasis. Nat Cell Biol. 1999;1:209–16.
Gross A, McDonald JM, Stanely J, Korsmeyer J. Bcl-2 family members and the mitochondria in apoptosis. Genes Dev. 1999;13:1899–911.
Luo Y, Zhou H, Mizutani M, Mizutani N, Reisfeld RA, Xiang R. Transcription factor Fos-related antigen 1 is an effective target for a breast cancer vaccine. Proc Natl Acad Sci U S A. 2003;100:8850–5.
Yu C, Chen K, Zheng H, Guo X, Jia W, Li M, et al. Overexpression of astrocyte elevated gene-1 (AEG-1) is associated with esophageal squamous cell carcinoma (ESCC) progression and pathogenesis. Carcinogenesis. 2009;30:894–901.
Kikuno N, Shiina H, Urakami S, Kawamoto K, Hirata H, Tanaka Y, et al. Knockdown of astrocyte-elevated gene-1 inhibits prostate cancer progression through upregulation of FOXO3a activity. Oncogene. 2007;26:7647–55.
Emdad L, Sarkar D, Su ZZ, Randolph A, Boukerche H, Valerie K, et al. Activation of the nuclear factor kappaB pathway by astrocyte elevated gene-1: implications for tumor progression and metastasis. Cancer Res. 2006;66:1509–16.
Lee SG, Su ZZ, Emdad L, Sarkar D, Fisher PB. Astrocyte elevated gene-1 (AEG-1) is a target gene of oncogenic Ha-rasrequiring phosphatidylinositol 3-kinase and c-Myc. Proc Natl Acad Sci U S A. 2006;103:17390–5.
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This work was supported by the National Science Foundation of China (No. 81201779) and Wu Jieping Medical Fund (No. 320.6750.1264).
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Yanmei Zou and Xiaomin Qin contributed equally to this work.
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Zou, Y., Qin, X., Xiong, H. et al. Apoptosis of human non-small-cell lung cancer A549 cells triggered by evodiamine through MTDH-dependent signaling pathway. Tumor Biol. 36, 5187–5193 (2015). https://doi.org/10.1007/s13277-015-3174-z
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DOI: https://doi.org/10.1007/s13277-015-3174-z