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Genistein and β-carotene enhance the growth-inhibitory effect of trichostatin A in A549 cells

  • Original Contribution
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European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Background

The combination of anti-cancer drugs with nutritional factors is a potential strategy for improving the efficacy and decreasing the toxicity of chemotherapy. However, whether nutritional factors enhance the effect of trichostatin A (TSA), a novel anti-cancer drug, is unclear.

Aim

We investigated the individual enhancing effect and its possible mechanisms of genistein, daidzein, β-carotene, retinoic acid, and α-tocopherol on the cell-growth-inhibitory effect of TSA in a human lung carcinoma cell line, A549.

Methods

A549 cells were incubated with TSA (50 ng/mL) alone or in combination with the various nutritional factors for various times, and cell growth was measured. IMR90 cells, human lung fibroblasts, were also incubated with TSA alone or in combination with genistein or β-carotene to determine the selectivity of these treatments. In addition, we studied effects on the cell cycle, caspase-3 activity, and DNA damage (by comet assay) in A549 cells.

Results

After treatment for 72 h, 10-μM genistein or β-carotene significantly enhanced the growth-inhibitory effect of TSA in A549 cells. Daidzein, retinoic acid, and α-tocopherol at the same concentration had no significant effect. However, genistein and β-carotene failed to enhance the cell-growth-arrest effect of TSA in IMR90 cells. Flow cytometric analysis showed that both genistein and β-carotene significantly increased the TSA-induced apoptosis in A549 cells. Genistein significantly enhanced TSA-induced caspase-3 activity in A549 cells by 34% at 24 h, and the caspase-3 inhibitor partly inhibited the enhancing effect of genistein on TSA-induced apoptosis. β-Carotene did not significantly affect TSA-induced caspase-3 activity. However, β-carotene rather than genistein enhanced TSA-induced DNA damage.

Conclusions

Genistein and β-carotene enhance the cell-growth-arrest effect of TSA on A549 cells. Genistein exerts its effect, at least partly, by increasing caspase-3 activity; whereas β-carotene may enhance TSA-induced cell death mainly through a caspase-3-independent pathway.

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References

  1. Chuang CH, Hu ML (2006) Synergistic DNA damage and lipid peroxidation in cultured human white blood cells exposed to 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone and ultraviolet A. Environ Mol Mutagen 47:73–81

    Article  CAS  Google Scholar 

  2. Collins AR, Ma AG, Duthie SJ (1995) The kinetics of repair of oxidative DNA damage (strand breaks and oxidised pyrimidines) in human cells. Mutat Res 336:69–77

    CAS  Google Scholar 

  3. Collins AR, Oscoz AA, Brunborg G, Gaivão I, Giovannelli L, Kruszewski M, Smith CC, Stetina R (2008) The comet assay: topical issues. Mutagenesis 23:143–151

    Article  CAS  Google Scholar 

  4. Divisi D, Di Tommaso S, Salvemini S, Garramone M, Crisci R (2006) Diet and cancer. Acta Biomed 77:118–123

    Google Scholar 

  5. Dokmanovic M, Marks PA (2005) Prospects: histone deacetylase inhibitors. J Cell Biochem 96:293–304

    Article  CAS  Google Scholar 

  6. de Kok TM, van Breda SG, Manson MM (2008) Mechanisms of combined action of different chemopreventive dietary compounds: a review. Eur J Nutr 47(Suppl 2):51–59

    Article  Google Scholar 

  7. Ganslmayer M, Ocker M, Zopf S, Leitner S, Hahn EG, Schuppan D, Herold C (2004) A quadruple therapy synergistically blocks proliferation and promotes apoptosis of hepatoma cells. Oncol Rep 11:943–950

    CAS  Google Scholar 

  8. Gardner CD, Chatterjee LM, Franke AA (2009) Effects of isoflavone supplements vs. soy foods on blood concentrations of genistein and daidzein in adults. J Nutr Biochem 20:227–234

    Article  CAS  Google Scholar 

  9. Hatayama H, Iwashita J, Kuwajima A, Abe T (2007) The short chain fatty acid, butyrate, stimulates MUC2 mucin production in the human colon cancer cell line, LS174T. Biochem Biophys Res Commun 356:599–603

    Article  CAS  Google Scholar 

  10. Henderson C, Mizzau M, Paroni G, Maestro R, Schneider C, Brancolini C (2003) Role of caspases, Bid, and p53 in the apoptotic response triggered by histone deacetylase inhibitors trichostatin-A (TSA) and suberoylanilide hydroxamic acid (SAHA). J Biol Chem 278:12579–12589

    Article  CAS  Google Scholar 

  11. Jin CY, Park C, Cheong J, Choi BT, Lee TH, Lee JD, Lee WH, Kim GY, Ryu CH, Choi TH (2007) Genistein sensitizes TRAIL-resistant human gastric adenocarcinoma AGS cells through activation of caspase-3. Cancer Lett 257:56–64

    Article  CAS  Google Scholar 

  12. Kim HR, Kim EJ, Yang SH, Jeong ET, Park C, Lee JH, Youn MJ, So HS, Park R (2006) Trichostatin A induces apoptosis in lung cancer cells via simultaneous activation of the death receptor-mediated and mitochondrial pathway. Exp Mol Med 38:616–624

    CAS  Google Scholar 

  13. Larsson SC, Bergkvist L, Naslund I, Rutegard J, Wolk A (2007) Vitamin A, retinol, and carotenoids and the risk of gastric cancer: a prospective cohort study. Am J Clin Nutr 85:497–503

    CAS  Google Scholar 

  14. Li J, Cheung HY, Zhang Z, Chan GK, Fong WF (2007) Andrographolide induces cell cycle arrest at G2/M phase and cell death in HepG2 cells via alteration of reactive oxygen species. Eur J Pharmacol 568:31–44

    Article  CAS  Google Scholar 

  15. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275

    CAS  Google Scholar 

  16. Mai Z, Blackburn GL, Zhou JR (2007) Soy phytochemicals synergistically enhance the preventive effect of tamoxifen on the growth of estrogen-dependent human breast carcinoma in mice. Carcinogenesis 28:1217–1223

    Article  CAS  Google Scholar 

  17. Mayne ST (1996) Beta-carotene, carotenoids, and disease prevention in humans. FASEB J 10:690–701

    CAS  Google Scholar 

  18. Mirzayans R, Scott A, Cameron M, Murray D (2004) Relationship between the radiosensitizing effect of wortmannin, DNA double-strand break rejoining, and p21WAF1 induction in human normal and tumor-derived cells. Mol Carcinog 39:164–172

    Article  CAS  Google Scholar 

  19. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63

    Article  CAS  Google Scholar 

  20. Nagata Y, Sonoda T, Mori M, Miyanaga N, Okumura K, Goto K, Naito S, Fujimoto K, Hirao Y, Takahashi A, Tsukamoto T, Akaza H (2007) Dietary isoflavones may protect against prostate cancer in Japanese men. J Nutr 137:1974–1979

    CAS  Google Scholar 

  21. Norbury CJ, Zhivotovsky B (2004) DNA damage-induced apoptosis. Oncogene 23:2797–2808

    Article  CAS  Google Scholar 

  22. Pfahl M (1998) Retinoid related molecules: new promises against lung and breast cancer. Expert Opin Investig Drugs 7:601–606

    Article  CAS  Google Scholar 

  23. Phillips HJ (1973) Dye exclusion tests for cell viability. In tissue culture, method and applications. Academic Press, London

    Google Scholar 

  24. Platta CS, Greenblatt DY, Kunnimalaiyaan M, Chen H (2007) The HDAC inhibitor trichostatin A inhibits growth of small cell lung cancer cells. J Surg Res 142:219–226

    Article  CAS  Google Scholar 

  25. Pong RC, Roark R, Ou JY, Fan J, Stanfield J, Frenkel E, Sagalowsky A, Hsieh JT (2006) Mechanism of increased coxsackie and adenovirus receptor gene expression and adenovirus uptake by phytoestrogen and histone deacetylase inhibitor in human bladder cancer cells and the potential clinical application. Cancer Res 66:8822–8828

    Article  CAS  Google Scholar 

  26. Roh MS, Kim CW, Park BS, Kim GC, Jeong JH, Kwon HC, Suh DJ, Cho KH, Yee SB, Yoo YH (2004) Mechanism of histone deacetylase inhibitor trichostatin A induced apoptosis in human osteosarcoma cells. Apoptosis 9:583–589

    Article  CAS  Google Scholar 

  27. Salgo MG, Cueto R, Winston GW, Pryor WA (1999) Beta carotene and its oxidation products have different effects on microsome mediated binding of benzo[a]pyrene to DNA. Free Radic Biol Med 26:162–173

    Article  CAS  Google Scholar 

  28. Sonnemann J, Hartwig M, Plath A, Saravana Kumar K, Muller C, Beck JF (2006) Histone deacetylase inhibitors require caspase activity to induce apoptosis in lung and prostate carcinoma cells. Cancer Lett 232:148–160

    Article  CAS  Google Scholar 

  29. Stahl W, Junghans A, de Boer B, Driomina ES, Briviba K, Sies H (1998) Carotenoid mixtures protect multilamellar liposomes against oxidative damage: synergistic effects of lycopene and lutein. FEBS Lett 427:305–308

    Article  CAS  Google Scholar 

  30. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group (1994) The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 330:1029–1035

    Article  Google Scholar 

  31. Touillaud MS, Thiebaut AC, Fournier A, Niravong M, Boutron-Ruault MC, Clavel-Chapelon F (2007) Dietary lignan intake and postmenopausal breast cancer risk by estrogen and progesterone receptor status. J Natl Cancer Inst 99:475–486

    Article  CAS  Google Scholar 

  32. van Helden YG, Keijer J, Knaapen AM, Heil SG, Briedé JJ, van Schooten FJ, Godschalk RW (2009) beta-Carotene metabolites enhance inflammation-induced oxidative DNA damage in lung epithelial cells. Free Radic Biol Med 46:299–304

    Article  Google Scholar 

  33. Weinstein SJ, Wright ME, Lawson EA, Snyder K, Mannisto S, Taylor PR, Virtamo J, Albanes D (2007) Serum and dietary vitamin E in relation to prostate cancer risk. Cancer Epidemiol Biomarkers Prev 16:1253–1259

    Article  CAS  Google Scholar 

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Acknowledgment

This research was supported by Grants (NSC-94-2320-B040-036) from the National Science Council, Republic of China.

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Authors and Affiliations

  1. Department of Beauty Science, Chienkao Technology University, Changhua, Taiwan, ROC

    Rong-Jen Shiau

  2. Institute of Nutritional Science, Chung Shan Medical University, No. 110 Sec 1 Jianguo N. Rd, Taichung, Taiwan, ROC

    Kai-Yong Chen & Shu-Lan Yeh

  3. Department of Biology, National Changhua University of Education, Changhua, Taiwan, ROC

    Yu-Der Wen

  4. Department of Food and Nutrition, Hungkuang University, Taichung County, Taiwan, ROC

    Cheng-Hung Chuang

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  1. Rong-Jen Shiau
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  2. Kai-Yong Chen
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Correspondence to Shu-Lan Yeh.

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Shiau, RJ., Chen, KY., Wen, YD. et al. Genistein and β-carotene enhance the growth-inhibitory effect of trichostatin A in A549 cells. Eur J Nutr 49, 19–25 (2010). https://doi.org/10.1007/s00394-009-0044-8

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  • DOI: https://doi.org/10.1007/s00394-009-0044-8

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