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Anti-proliferate and pro-apoptotic effects of 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyranone through inactivation of NF-κB in Human Colon Cancer Cells

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Abstract

Many natural compounds have been shown to prevent cancer cell growth through the redox regulation of transcription factors. NF-κB, a redox transcription factor, has been implicated in the apoptotic cell death of several cancer cells. This study examined whether or nor 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyranone (DDMP) isolated from onions can modulate the activity of NF-κB, thereby induce the apoptotic cell death of colon cancer cells. Treatment with different DDMP concentrations (0.5–1.5 mg/mL) for various periods (0–48 h) inhibited the growth of colon cancer cells (SW620 and HCT116) followed by the induction of apoptosis in a dose dependent manner. It was also found that DDMP modulated tumor necrosis factor-α (TNF-α) and tetradeanoyl phorbol acetate (TPA)-induced NF-κB transcriptional and DNA binding activity. Moreover, DDMP suppressed the NF-κB target anti-apoptotic genes (Bcl-2), whereas it induced the expression of the apoptotic genes (Bax, cleaved caspase-3 and cleaved PARP). These results suggest that DDMP from onions inhibit colon cancer cell growth by inducing apoptotic cell death through the inhibition of NF-κB.

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References

  • Aggarwal, S., Ichikawa, H., Takada, Y., Sandur, S. K., Shishodia, S., and Aggarwal, B. B., Curcumin (diferuloylmethane) down- regulates expression of cell proliferation and antiapoptotic and metastatic gene products through suppression of IkappaBalpha kinase and Akt activation.Mol. Pharmacol., 69, 195–206 (2006).

    PubMed  CAS  Google Scholar 

  • Berhow, M. A., Wagner, E. D., Vaughn, S. F., and Plewa, M. J., Characterization and antimutagenic activity of soybean saponins.Mutat. Res., 448, 11–22 (2000).

    PubMed  CAS  Google Scholar 

  • Burkhard, H., NF-kB: arresting a major culprit in cancer.Drug Discov. Today, 7, 653–663 (2002).

    Article  Google Scholar 

  • Daveby, Y. D., Aman, P., Betz, J. M., and Musser, S. M., Effect of storage and extraction on the ratio of soyasaponin I to 2, 3- dihydro-2,5-dihydroxy-6-methyl-4-pyrone-conjugated soyasaponin I in dehulled peas (Pisum sativum L).J. Sci. Food Agric., 78, 141–146 (1998).

    Article  CAS  Google Scholar 

  • Fukushima, S., Takada, N., Hori, T., and Wanibuchi, H., Cancer prevention by organosulfur compounds from garlic and onion.J. Cell Biochem., 27, 100–105 (1997).

    Article  CAS  Google Scholar 

  • Galeone, C., Pelucchi, C., Levi, F., Negri, E., Franceschi, S., Talamini, R., Giacosa, A., and La Vecchia,C., Onion and garlic use and human cancer.Am. J. Clin. Nutr., 84, 1027–1032 (2006).

    PubMed  CAS  Google Scholar 

  • Hardwick, J. C., Van den, Brink, G. R., Offerhaus, G. J., Van Deventer, S. J., and Peppelenbosch, M. P., NF-kB, p38 MAPK and JNK are highly expressed and active in the stroma of human colonic adenomatous polyps.Oncogene, 20, 819–827 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Huang, S., Pettaway, C. A., Uehara, H., Bucana, C. D., and Fidler, I. J., Blockade of NF-kB activity in human prostate cancer cells is associated with suppression of angiogenesis, invasion, and metastasis.Oncogene, 20, 4188–4197 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Jiang, J., Slivova, V., and Sliva, D., Ganoderma lucidum inhibits proliferation of human breast cancer cells by down-regulation of estrogen receptor and NF-kappaB signaling.Int. J. Oncol., 29, 695–703 (2006).

    PubMed  CAS  Google Scholar 

  • Karin, M., Cao, Y., Greten, F. R., and Li, Z. W., NF-kB in cancer: from innocent by stander to major culprit.Nat. Rev. Drug Discov., 2, 301–310. (2002).

    Article  CAS  Google Scholar 

  • Kim, H., Hall, P., Smith, M., Kirk, M., Prasain, J. K., Barnes, S., and Grubbs, C., Chemoprevention by grape seed extract and genistein in carcinogen-induced mammary cancer in rats is diet dependent.J. Nutr., 12, 3445–3452 (2004).

    Google Scholar 

  • Lee, S. H., Lee, C. W., Lee, J. W., Choi, M. S., Son, D. J., Chung, Y. B., Lee, C. K., Oh, K. W., Moon, D. C., Kown, B. M., and Hong, J. T., Induction of apoptotic cell death by 2′- hydroxycinnamaldehyde is involved with ERK-dependent inactivation of NF-kappaB in TNF-alpha-treated SW620 colon cancer cells.Biochem. Pharmacol., 70, 1147–1157 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Leighton, T., Ginther, C., Fluss, L., Harter, W. K., Cansado, J., and Notario, V., Molecular characterization of quercetin and quercetin glycosides inAllium vegetables. In: Phenolic compounds and their effects on human health II.Am. Chem. Society., 507, 220–238 (1992).

    CAS  Google Scholar 

  • Liang, M. C., Bardhan, S., Pace, E. A., Rosman, D., Beutler, J. A., Porco, J. A., and Gilmore, T. D., Inhibition of transcription factor NF-kappaB signaling proteins IKKbeta and p65 through specific cysteine residues by epoxyquinone A monomer: correlation with its anti-cancer cell growth activity.Biochem. Pharmacol., 71, 634–645 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Lind, D. S., Hochwald, S. N., Malaty, J., Rekkas, S., Hebig, P., Mishra, G., Moldawer, L. L., Copeland, E. M., and Mackat, S., Nuclear factor-B is upregulated in colorectal cancer.Surgery, 130, 363–369 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Niho, N., Mutoh, M., Sakano, K., Takahashi, M., Hirano, S., Nukaya, H., Sugimura, T., and Wakabayashi, K., Inhibition of intestinal carcinogenesis by a new flavone derivative, chafuroside, in oolong tea.Cancer Sci., 97, 248–251 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Pierce, J. D., Pierce, J., Stremming, S., Fakhari, M., and Clancy, R. L., The role of apoptosis in respiratory diseases.Clin. Nurse Spec., 21, 22–28 (2007).

    Article  PubMed  Google Scholar 

  • Plewa, M. J., Wagner, E. D., Berhow, M. A., Conway, A., Raybum, A. L., and Anderson, D., Antimutagenic activity of chemical fractions isolated from a commercial soybean processing byproduct.Teratog. Carcinog. Mutagen., 19, 121–135 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Quan, J., Yin, X., Jin, M., and Shen, M., Study on the inhibition of alpha-glucosidase by soyasaponins.Zhong Yao Cai., 26, 654–656 (2003).

    PubMed  Google Scholar 

  • Saccani, A., Schioppa, T., Porta, C., Biswas, S. K., Nebuloni, M., Vago, L., Bottazzi, B., Colombo, M. P., Mantovani, A., and Sica, A., p50 nuclear factor-kappaB overexpression in tumor- associated macrophages inhibits M1 inflammatory responses and antitumor resistance.Cancer Res., 66, 11432–11440 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Shishodia, S. and Aggarwal, B. B., Nuclear factor-kappaB: a friend or a foe in cancer?Biochem. Pharmacol., 68, 1071- 1080 (2004).

    Article  PubMed  CAS  Google Scholar 

  • Takara, K., Otsuka, K., Wada, K., Iwasaki, H., and Yamashita, M.. 1,1-Diphenyl-2-picrylhydrazyl radical scavenging activity and tyrosinase inhibitory effects of constituents of sugarcane molasses.Biosci. Biotechnol. Biochem., 71, 183–191 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Tang, X., Liu, D., Shishodia, S., Ozburn, N., Behrens, C., Lee, J. J., Hongm, W. K., Aggarwal, B. B., and Wistuba, I. I., Nuclear factor-kappaB (NF-kappaB) is frequently expressed in lung cancer and preneoplastic lesions.Cancer, 107, 2637–2646 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Teyssier, C., Amiot, M. J., Mondy, N., Auger, J., Kahane, R., and Siess, M. H., Effect of onion consumption by rats on hepatic drug-metabolizing enzymes.Food Chem. Toxicol., 39, 981- 987 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Wang, Y., Lee, K. W., Chan, F. L., Chen, S., and Leung, L. K., The red wine polyphenol resveratrol displays bilevel inhibition on aromatase in breast cancer cells.Toxicol. Sci., 92,71–77 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Yemelyanov, A., Gasparian, A., Lindholm, P., Dang, L., Pierce, J. W., Kisseljov, F., Karseladze, A., and Budunova, I., Effects of IKK inhibitor PS1145 on NF-kappaB function, proliferation, apoptosis and invasion activity in prostate carcinoma cells.Oncogene, 25, 387–398 (2006).

    PubMed  CAS  Google Scholar 

  • Yoshiki, Y., Kim, J. H., and Okubo, K. Saponins conjugated with 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one from Phaseolus coccineus.Phytochemistry, 36, 1009–1012 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Yoshiki, Y. and Okubo, K., Active Oxygen Scavenging Activity of DDMP (2,3-Dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one) Saponin in Soybean Seed.Biosci. Biotech. Biochem., 59, 1556–1557 (1995).

    Article  CAS  Google Scholar 

  • Young, M. R., Yang, H. S., and Colbum, N. H., Promising molecular targets for cancer prevention: AP-1, NF-κB and Pdcd4.Trends Mol. Med., 9, 36–41 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Yu, L. L., Yu, H. G., and Yu, J. P., Nuclear factor-kappaB p65 (RelA) transcription factor is constitutively activated in human colorectal carcinoma tissue.World J. Gastroenterol., 10, 3255–3260 (2004).

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. College of Agriculture, Life and Environments Sciences, Chungbuk National University, 361-763, Cheongju, Korea

    In Guk Hwang & Heon-Sang Jeong

  2. College of Veternary Medicine, Chungbuk National University, 361-763, Cheongju, Korea

    Tae Myoung Kim, Young Won Yoon & Dae Joong Kim

  3. Department of Food and Biotechnology, Chungju National University, 380-702, Chungju, Korea

    Ung Soo Lee

  4. Collage of Pharmacy, Chungbuk National University, 48, Gaesin-dong, Heunduk-gu, Cheungju, 361-763, Chungbuk, Korea

    Jung Ok Ban, Bang Yeon Hwang & Jin Tae Hong

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  1. Jung Ok Ban
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  2. In Guk Hwang
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  3. Tae Myoung Kim
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Correspondence to Jin Tae Hong.

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Ban, J.O., Hwang, I.G., Kim, T.M. et al. Anti-proliferate and pro-apoptotic effects of 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyranone through inactivation of NF-κB in Human Colon Cancer Cells. Arch Pharm Res 30, 1455–1463 (2007). https://doi.org/10.1007/BF02977371

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  • DOI: https://doi.org/10.1007/BF02977371

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