High concentrations of pyridoxal stimulate the expression of IGFBP1 in HepG2 cells through upregulation of the ERK/c‑Jun pathway

Zhang,Peipei; Suidasari,Sofya; Hasegawa,Tomomi; Yanaka,Noriyuki; Kato,Norihisa

doi:10.3892/mmr.2013.1629

High concentrations of pyridoxal stimulate the expression of IGFBP1 in HepG2 cells through upregulation of the ERK/c‑Jun pathway

Authors:
- Peipei Zhang
- Sofya Suidasari
- Tomomi Hasegawa
- Noriyuki Yanaka
- Norihisa Kato
View Affiliations

Affiliations: Graduate School of Biosphere Science, Hiroshima University, Higashi‑Hiroshima, Hiroshima 739‑8528, Japan
Published online on: August 14, 2013 https://doi.org/10.3892/mmr.2013.1629
Pages: 973-978

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Increasing evidence suggests that dietary vitamin B6 is linked to the prevention of cancer and cardiovascular disease. However, the molecular mechanisms involved in this process are not yet understood. Preliminary results in the current study indicated, following DNA microarray analysis and quantitative PCR, that insulin‑like growth factor‑binding protein 1 (IGFBP1) mRNA is upregulated in HT29 colon carcinoma cells exposed to pyridoxal (PL, 500 µM). IGFBP1 is secreted from the liver and is hypothesized to exert a protective role in the development of cancer and cardiovascular disease. Thus, further experiments were performed to investigate the effect of PL on the expression of IGFBP1 in HepG2 hepatocellular carcinoma cells. The addition of PL (500 µM) markedly increased the expression of IGFBP1 mRNA in HepG2 cells at 6, 12 and 24 h (P<0.01), whereas other vitamers (500 µM), including pyridoxal 5'‑phosphate (PLP), pyridoxine (PN) and pyridoxamine (PM), caused no such effect. The expression of the IGFBP1 protein in the cell lysate and culture medium was elevated in the presence of PL. PL elevated expression of the active form of ERK1 protein, p‑ERK1, and the p‑c‑Jun protein, a downstream factor of ERK. Furthermore, IGFBP1 expression, elevated by PL, was suppressed by PD98059, an ERK inhibitor. Higher expression of IGFBP1 protein by PL was suppressed by cycloheximide. These results suggest that PL may induce the expression of IGFBP1 in hepatoma cells via a mechanism involving the ERK/c‑Jun pathway.

View Figures

View References

1	Ishihara J, Otani T, Inoue M, Iwasaki M, Sasazuki S and Tsugane S; Japan Public Health Center-based Prospective Study Group. Low intake of vitamin B-6 is associated with increased risk of colorectal cancer in Japanese men. J Nutr. 137:1808–1814. 2007.PubMed/NCBI
2	Theodoratou E, Farrington SM, Tenesa A, McNeill G, Cetnarskyj R, Barnetson RA, Porteous ME, Dunlop MG and Campbell H: Dietary vitamin B6 intake and the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev. 17:171–182. 2008. View Article : Google Scholar : PubMed/NCBI
3	Larsson SC, Orsini N and Wolk A: Vitamin B6 and risk of colorectal cancer: a meta-analysis of prospective studies. JAMA. 303:1077–1083. 2010. View Article : Google Scholar : PubMed/NCBI
4	Zhang XH, Ma J, Smith-Warner SA, Lee JE and Giovannucci E: Vitamin B6 and colorectal cancer: current evidence and future directions. World J Gastroenterol. 19:1005–1010. 2013. View Article : Google Scholar : PubMed/NCBI
5	Komatsu SI, Watanabe H, Oka T, Tsuge H, Nii H and Kato N: Vitamin B-6-supplemented diets compared with a low vitamin B-6 diet suppress azoxymethane-induced colon tumorigenesis in mice by reducing cell proliferation. J Nutr. 131:2204–2207. 2001.PubMed/NCBI
6	Komatsu S, Watanabe H, Oka T, Tsuge H and Kat N: Dietary vitamin B6 suppresses colon tumorigenesis, 8-hydroxyguanosine, 4-hydroxynonenal, and inducible nitric oxide synthase protein in azoxymethane-treated mice. J Nutr Sci Vitaminol (Tokyo). 48:65–68. 2002. View Article : Google Scholar : PubMed/NCBI
7	Komatsu S, Yanaka N, Matsubara K and Kato N: Antitumor effect of vitamin B6 and its mechanisms. Biochim Biophys Acta. 1647:127–130. 2003. View Article : Google Scholar : PubMed/NCBI
8	Kayashima T, Tanaka K, Okazaki Y, Matsubara K, Yanaka N and Kato N: Consumption of vitamin B6 reduces colonic damage and protein expression of HSP70 and HO-1, the anti-tumor targets, in rats exposed to 1,2-dimethylhydrazine. Oncol Lett. 2:1243–1246. 2011.PubMed/NCBI
9	Yanaka N, Koyama TA, Komatsu S, Nakamura E, Kanda M and Kato N: Vitamin B6 suppresses NF-kappaB activation in LPS-stimulated mouse macrophages. Int J Mol Med. 16:1071–1075. 2005.PubMed/NCBI
10	Diffley JF: Affinity labeling the DNA polymerase alpha complex. I. Pyridoxal 5′-phosphate inhibition of DNA polymerase and DNA primase activities of the DNA polymerase alpha complex from Drosophila melanogaster embryos. J Biol Chem. 263:14669–14677. 1988.
11	Matsubara K, Matsumoto H, Mizushina Y, Lee JS and Kato N: Inhibitory effect of pyridoxal 5′-phosphate on endothelial cell proliferation, replicative DNA polymerase and DNA topoisomerase. Int J Mol Med. 12:51–55. 2003.
12	Martial J, Zaldivar J, Bull P, Venegas A and Valenzuela P: Inactivation of rat liver RNA polymerases I and II and yeast RNA polymerase I by pyridoxal 5′-phosphate. Evidence for the participation of lysyl residues at the active site. Biochemistry. 14:4907–4911. 1975.PubMed/NCBI
13	Vermeersch JJ, Christmann-Franck S, Karabashyan LV, Fermandjian S, Mirambeau G and Der Garabedian PA: Pyridoxal 5′-phosphate inactivates DNA topoisomerase IB by modifying the lysine general acid. Nucleic Acids Res. 32:5649–5657. 2004.
14	Matsubara K, Mori M, Matsuura Y and Kato N: Pyridoxal 5′-phosphate and pyridoxal inhibit angiogenesis in serum-free rat aortic ring assay. Int J Mol Med. 8:505–508. 2001.
15	Lee PD, Giudice LC, Conover CA and Powell DR: Insulin-like growth factor binding protein-1: recent findings and new directions. Proc Soc Exp Biol Med. 216:319–357. 1997. View Article : Google Scholar : PubMed/NCBI
16	Yee D, Jackson JG, Kozelsky TW and Figueroa JA: Insulin-like growth factor binding protein 1 expression inhibits insulin-like growth factor I action in MCF-7 breast cancer cells. Cell Growth Differ. 5:73–77. 1994.PubMed/NCBI
17	Van den Berg CL, Cox GN, Stroh CA, Hilsenbeck SG, Weng CN, McDermott MJ, Pratt D, Osborne CK, Coronado-Heinsohn EB and Yee D: Polyethylene glycol conjugated insulin-like growth factor binding protein-1 (IGFBP-1) inhibits growth of breast cancer in athymic mice. Eur J Cancer. 33:1108–1113. 1997.PubMed/NCBI
18	Zhang X and Yee D: Insulin-like growth factor binding protein-1 (IGFBP-1) inhibits breast cancer cell motility. Cancer Res. 62:4369–4375. 2002.PubMed/NCBI
19	Ngo TH, Barnard RJ, Leung PS, Cohen P and Aronson WJ: Insulin-like growth factor I (IGF-I) and IGF binding protein-1 modulate prostate cancer cell growth and apoptosis: possible mediators for the effects of diet and exercise on cancer cell survival. Endocrinology. 144:2319–2324. 2003. View Article : Google Scholar : PubMed/NCBI
20	Wei EK, Ma J, Pollak MN, Rifai N, Fuchs CS, Hankinson SE and Giovannucci E: A prospective study of C-peptide, insulin-like growth factor-I, insulin-like growth factor binding protein-1, and the risk of colorectal cancer in women. Cancer Epidemiol Biomarkers Prev. 14:850–855. 2005. View Article : Google Scholar : PubMed/NCBI
21	Le Marchand L, Wang H, Rinaldi S, Kaaks R, Vogt TM, Yokochi L and Decker R: Associations of plasma C-peptide and IGFBP1 levels with risk of colorectal adenoma in a multiethnic population. Cancer Epidemiol Biomarkers Prev. 19:1471–1477. 2010.PubMed/NCBI
22	Rajwani A, Ezzat V, Smith J, Yuldasheva NY, Duncan ER, Gage M, Cubbon RM, Kahn MB, Imrie H, Abbas A, Viswambharan H, Aziz A, Sukumar P, Vidal-Puig A, Sethi JK, Xuan S, Shah AM, Grant PJ, Porter KE, Kearney MT and Wheatcroft SB: Increasing circulating IGFBP1 levels improves insulin sensitivity, promotes nitric oxide production, lowers blood pressure, and protects against atherosclerosis. Diabetes. 61:915–924. 2012. View Article : Google Scholar
23	Taub R: Liver regeneration 4: transcriptional control of liver regeneration. FASEB J. 10:413–427. 1996.PubMed/NCBI
24	Leu JI, Crissey MA, Craig LE and Taub R: Impaired hepatocyte DNA synthetic response posthepatectomy in insulin-like growth factor binding protein 1-deficient mice with defects in C/EBP beta and mitogen-activated protein kinase/extracellular signal-regulated kinase regulation. Mol Cell Biol. 23:1251–1259. 2003. View Article : Google Scholar
25	Ink SL and Henderson LM: Vitamin B6 metabolism. Ann Rev Nutr. 4:455–470. 1984. View Article : Google Scholar
26	Nakari M, Kanouchi H and Oka T: High dose of pyridoxine induces IGFBP-3 mRNA expression in MCF-7 cells and its induction is inhibited by the p53-specific inhibitor pifithrin-α. J Nutr Sci Vitaminol (Tokyo). 57:280–284. 2011.PubMed/NCBI
27	Frost RA, Nystrom GJ and Lang CH: Stimulation of insulin-like growth factor binding protein-1 synthesis by interleukin-1beta: requirement of the mitogen-activated protein kinase pathway. Endocrinology. 141:3156–3164. 2000.PubMed/NCBI
28	Leu JI, Crissey MA, Leu JP, Ciliberto G and Taub R: Interleukin-6-induced STAT3 and AP-1 amplify hepatocyte nuclear factor 1-mediated transactivation of hepatic genes, an adaptive response to liver injury. Mol Cell Biol. 21:414–424. 2001. View Article : Google Scholar : PubMed/NCBI
29	Magne L, Blanc E, Marchand A, Fafournoux P, Barouki R, Rouach H and Garlatti M: Stabilization of IGFBP1 mRNA by ethanol in hepatoma cells involves the JNK pathway. J Hepatol. 47:691–698. 2007. View Article : Google Scholar : PubMed/NCBI
30	Kanouchi H, Shibuya M, Tsukamoto S, Fujimura Y, Tachibana H, Yamada K and Oka T: Comparisons of uptake and cell surface binding among pyridoxal, pyridoxine, and pyridoxamine in RAW264.7 cells. Nutrition. 26:648–652. 2010. View Article : Google Scholar : PubMed/NCBI
31	Lumeng L, Brashear RE and Li TK: Pyridoxal 5′-phosphate in plasma: source, protein-binding, and cellular transport. J Lab Clin Med. 84:334–343. 1974.
32	Anderson BB, O’Brien H, Griffin GE and Mollin DL: Hydrolysis of pyridoxal-5′-phosphate in plasma in conditions with raised alkaline phosphate. Gut. 21:192–194. 1980.
33	Sakurai T, Asakura T, Mizuno A and Matsuda M: Absorption and metabolism of pyridoxamine in mice. I. Pyridoxal as the only form of transport in blood. J Nutr Sci Vitaminol (Tokyo). 37:341–348. 1991. View Article : Google Scholar : PubMed/NCBI
34	Leppä S, Saffrich R, Ansorge W and Bohmann D: Differential regulation of c-Jun by ERK and JNK during PC12 cell differentiation. EMBO J. 17:4404–4413. 1998.PubMed/NCBI
35	Shen J, Lai CQ, Mattei J, Ordovas JM and Tucker KL: Association of vitamin B-6 status with inflammation, oxidative stress, and chronic inflammatory conditions: the Boston Puerto Rican Health Study. Am J Clin Nutr. 91:337–342. 2010. View Article : Google Scholar : PubMed/NCBI