Tangeretin and its metabolite 4′-hydroxytetramethoxyflavone attenuate EGF-stimulated cell cycle progression in hepatocytes; Role of inhibition at the level of mTOR/p70S6K

British Journal of Pharmacology

Volumn 162, Issue 8, 2011, Pages 1781-1791

  Cheng, Z ^a   Surichan, S ^a   Ruparelia, K ^a   Arroo, R ^a   Boarder, M R ^a  

^a DE MONTFORT UNIVERSITY   (United Kingdom)

Author keywords

Akt; cancer; hepatocyte; mTOR; p70S6K; S6K; tangeretin

Indexed keywords

4' HYDROXY 5,6,7,8 TETRAMETHOXYFLAVONE; CELL DNA; CYTOCHROME P450 1A; EPIDERMAL GROWTH FACTOR; MAMMALIAN TARGET OF RAPAMYCIN; NATURAL PRODUCT; PROTEIN KINASE B; S6 KINASE; TANGERETIN; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CELL CYCLE PROGRESSION; CELL CYCLE S PHASE; CELL STIMULATION; CELL VIABILITY; CONCENTRATION RESPONSE; CONTROLLED STUDY; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; FOOD COMPOSITION; LIVER CELL; LIVER MICROSOME; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; SIGNAL TRANSDUCTION;

ANIMALS; ANTINEOPLASTIC AGENTS, PHYTOGENIC; CELL CYCLE; CELL SURVIVAL; DOSE-RESPONSE RELATIONSHIP, DRUG; EPIDERMAL GROWTH FACTOR; FLAVONES; HEPATOCYTES; HUMANS; MALE; PHOSPHORYLATION; PRODRUGS; RATS; RATS, WISTAR; RIBOSOMAL PROTEIN S6 KINASES, 70-KDA; TOR SERINE-THREONINE KINASES;

EID: 79953036316     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2010.01185.x     Document Type: Article

References (29)

1. Androutsopoulos V, Arroo RR, Hall JF, Surichan S, Potter GA, (2008). Antiproliferative and cytostatic effects of the natural product eupatorin on MDA-MB-468 human breast cancer cells due to CYP1-mediated metabolism. Breast Cancer Res 10: R39.
2. Androutsopoulos VP, Ruparelia K, Arroo RR, Tsatsakis AM, Spandidos DA, (2009). CYP1-mediated antiproliferative activity of dietary flavonoids in MDA-MB-468 breast cancer cells. Toxicology 264: 162-170.
3. Arafa el SA, Zhu Q, Barakat BM, Wani G, Zhao Q, El-Mahdy MA, et al,. (2009). Tangeretin sensitizes cisplatin-resistant human ovarian cancer cells through downregulation of phosphoinositide 3-kinase/Akt signaling pathway. Cancer Res 69: 8910-8917.
4. Brachmann S, Fritsch C, Maira SM, Garcia-Echeverria C, (2009). PI3K and mTOR inhibitors: a new generation of targeted anticancer agents. Curr Opin Cell Biol 21: 194-198.
5. Breinholt VM, Offord EA, Brouwer C, Nielsen SE, Brosen K, Friedberg T, (2002). In vitro investigation of cytochrome P450-mediated metabolism of dietary flavonoids. Food Chem Toxicol 40: 609-616. (Pubitemid 34310426)
6. Breinholt VM, Rasmussen SE, Brosen K, Friedberg TH, (2003). In vitro metabolism of genistein and tangeretin by human and murine cytochrome P450s. Pharmacol Toxicol 93: 14-22. (Pubitemid 36819369)
7. Chen KH, Weng MS, Lin JK, (2007). Tangeretin suppresses IL-1beta-induced cyclooxygenase (COX)-2 expression through inhibition of p38 MAPK, JNK, and AKT activation in human lung carcinoma cells. Biochem Pharmacol 73: 215-227.
8. Chen P, Yan H, Chen Y, He Z, (2009). The variation of AkT/TSC1-TSC1/mTOR signal pathway in hepatocytes after partial hepatectomy in rats. Exp Mol Pathol 86: 101-107.
9. Coutant A, Rescan C, Gilot D, Loyer P, Guguen-Guillouzo C, Baffet G, (2002). PI3K-FRAP/mTOR pathway is critical for hepatocyte proliferation whereas MEK/ERK supports both proliferation and survival. Hepatology 36: 1079-1088. (Pubitemid 35253423)
10. Dixon CJ, White PJ, Hall JF, Kingston S, Boarder MR, (2005). Regulation of human hepatocytes by P2Y receptors: control of glycogen phosphorylase, Ca2+, and mitogen-activated protein kinases. J Pharmacol Exp Ther 313: 1305-1313. (Pubitemid 40727036)
11. Efeyan A, Sabatini DM, (2010). mTOR and cancer: many loops in one pathway. Curr Opin Cell Biol 22: 169-176.
12. Fausto N, Campbell JS, Riehle KJ, (2006). Liver regeneration. Hepatology 43 (Suppl. 1): S45-S53.
13. Hirano T, Abe K, Gotoh M, Oka K, (1995). Citrus flavone tangeretin inhibits leukaemic HL-60 cell growth partially through induction of apoptosis with less cytotoxicity on normal lymphocytes. Br J Cancer 72: 1380-1388. (Pubitemid 26002646)
14. Laplante M, Sabatini DM, (2009). mTOR signaling at a glance. J Cell Sci 122: 3589-3594.
15. Laplante M, Sabatini DM, (2010). mTORC1 activates SREBP-1c and uncouples lipogenesis from gluconeogenesis. Proc Natl Acad Sci U S A 107: 3281-3282.
16. Loyer P, Cariou S, Glaise D, Bilodeau M, Baffet G, Guguen-Guillouzo C, (1996). Growth factor dependence of progression through G1 and S phases of adult rat hepatocytes in vitro. Evidence of a mitogen restriction point in mid-late G1. J Biol Chem 271: 11484-11492.
17. Luo Y, Dixon CJ, Hall JF, White PJ, Boarder MR, (2007). A role for Akt in epidermal growth factor-stimulated cell cycle progression in cultured hepatocytes: generation of a hyperproliferative window after adenoviral expression of constitutively active Akt. J Pharmacol Exp Ther 321: 884-891. (Pubitemid 46762686)
18. Murray GI, Taylor MC, McFadyen MC, McKay JA, Greenlee WF, Burke MD, et al,. (1997). Tumor-specific expression of cytochrome P450 CYP1B1. Cancer Res 57: 3026-3031. (Pubitemid 27315056)
19. Morley KL, Ferguson PJ, Koropatnick J, (2007). Tangeretin and nobiletin induce G1 cell cycle arrest but not apoptosis in human breast and colon cancer cells. Cancer Lett 251: 168-178. (Pubitemid 46589774)
20. Nielsen SE, Breinholt V, Cornett C, Dragsted LO, (2000). Biotransformation of the citrus flavone tangeretin in rats. Identification of metabolites with intact flavane nucleus. Food Chem Toxicol 38: 739-746. (Pubitemid 30628868)
21. Pan MH, Chen WJ, Lin-Shiau SY, Ho CT, Lin JK, (2002). Tangeretin induces cell-cycle G1 arrest through inhibiting cyclin-dependent kinases 2 and 4 activities as well as elevating Cdk inhibitors p21 and p27 in human colorectal carcinoma cells. Carcinogenesis 23: 1677-1684.
22. Parent R, Kolippakkam D, Booth G, Beretta L, (2007). Mammalian target of rapamycin activation impairs hepatocytic differentiation and targets genes moderating lipid homeostasis and hepatocellular growth. Cancer Res 67: 4337-4345. (Pubitemid 46815082)
23. Planchard D, Loriot Y, Goubar A, Commo F, Soria JC, (2009). Differential expression of biomarkers in men and women. Semin Oncol 36: 553-565.
24. Scheving LA, Stevenson MC, Zhang X, Russell WE, (2008). Cultured rat hepatocytes upregulate Akt and ERK in an ErbB-2-dependent manner. Am J Physiol Gastrointest Liver Physiol 295: G322-G331.
25. Sophie L, (2005). Tangeretin induces caspase dependetn apoptosis and G2/M arrest in the erythroleukaemia cell line, MCF-10. Blood 106: 4435.
26. Subramanian A, Salhab M, Mokbel K, (2008). Oestrogen producing enzymes and mammary carcinogenesis: a review. Breast Cancer Res Treat 111: 191-202.
27. Thoresen GH, Guren TK, Christoffersen T, (2003). Role of ERK, p38 and Pl3-kinase in EGF receptorMediated mitogenic signalling in cultured rat hepatocytes: Requirement for sustained ERK activation. Cell Physiol Biochem 13: 229-238. (Pubitemid 36921042)
28. Van Slambrouck S, Parmar VS, Sharma SK, De Bondt B, Fore F, Coopman P, et al,. (2005). Tangeretin inhibits extracellular-signal-regulated kinase (ERK) phosphorylation. FEBS Lett 579: 1665-1669. (Pubitemid 40341540)
29. Walle T, (2007). Methoxylated flavones, a superior cancer chemopreventive flavonoid subclass? Semin Cancer Biol 17: 354-362. (Pubitemid 47369171)