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3-Hydroxyflavanone induces apoptosis in HeLa cells

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Abstract

Flavonoids and their derivatives exhibit many biological properties, including anti-inflammatory and antitumor activities. However, the antitumor action of 3′-hydroxyflavanone (3′-HF) is largely unknown. Antitumor efficacy of 3′-HF was assessed using cervical cancer (HeLa) cells. 3′-HF treatment resulted in a reduction in cell proliferation. A flow cytometric analysis demonstrated that 3′-HF deregulated cell cycle progression and triggered apoptosis. 3′-HF also increased the levels of p53 and p21, but decreased the level of cyclin D1. 3′-HF-induced apoptosis was accompanied by poly(ADP-ribose)polymerase cleavage. Together, these data indicate that 3′-HF possesses antitumor activity, which is mediated via the deregulation of cell cycle progression and induction of apoptosis.

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References

  • Araujo JR, Goncalves P, and Martel F (2011) Chemopreventive effect of dietary polyphenols in colorectal cancer cell lines. Nutr Res 31, 77–87.

    Article  CAS  Google Scholar 

  • Beier F, Taylor AC, and LuValle P (1999) The Raf-1/MEK/ERK pathway regulates the expression of the p21(Cip1/Waf1) gene in chondrocytes. J Biol Chem 274, 30273–30279.

    Article  CAS  Google Scholar 

  • Bunz F, Dutriaux A, Lengauer C, Waldman T, Zhou S, Brown JP et al. (1998) Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science 282, 1497–1501.

    Article  CAS  Google Scholar 

  • Ciccarelli C, Marampon F, Scoglio A, Mauro A, Giacinti C, De Cesaris P et al. (2005) p21WAF1 expression induced by MEK/ERK pathway activation or inhibition correlates with growth arrest, myogenic differentiation and onco-phenotype reversal in rhabdomyosarcoma cells. Mol Cancer 4, 41.

    Article  Google Scholar 

  • Datto MB, Li Y, Panus JF, Howe DJ, Xiong Y, and Wang XF (1995) Transforming growth factor beta induces the cyclin-dependent kinase inhibitor p21 through a p53-independent mechanism. Proc Natl Acad Sci USA 92, 5545–5549.

    Article  CAS  Google Scholar 

  • de Siervi A, Marinissen M, Diggs J, Wang XF, Pages G, and Senderowicz A (2004) Transcriptional activation of p21(waf1/cip1) by alkylphospholipids: role of the mitogen-activated protein kinase pathway in the transactivation of the human p21(waf1/cip1) promoter by Sp1. Cancer Res 64, 743–750.

    Article  Google Scholar 

  • Deep G, Singh RP, Agarwal C, Kroll DJ, and Agarwal R (2006) Silymarin and silibinin cause G1 and G2-M cell cycle arrest via distinct circuitries in human prostate cancer PC3 cells: a comparison of flavanone silibinin with flavanolignan mixture silymarin. Oncogene 25, 1053–1069.

    Article  CAS  Google Scholar 

  • Dent P, Yacoub A, Fisher PB, Hagan MP, and Grant S (2003) MAPK pathways in radiation responses. Oncogene 22, 5885–5896.

    Article  CAS  Google Scholar 

  • el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM et al. (1993) WAF1, a potential mediator of p53 tumor suppression. Cell 75, 817–825.

    Article  CAS  Google Scholar 

  • Facchinetti MM, De Siervi A, Toskos D, and Senderowicz AM (2004) UCN-01-induced cell cycle arrest requires the transcriptional induction of p21(waf1/cip1) by activation of mitogen-activated protein/extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase pathway. Cancer Res 64, 3629–3637.

    Article  CAS  Google Scholar 

  • Harper JW, Adami GR, Wei N, Keyomarsi K, and Elledge SJ (1993) The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell 75, 805–816.

    Article  CAS  Google Scholar 

  • Knekt P, Jarvinen R, Seppanen R, Hellovaara M, Teppo L, Pukkala E et al. (1997) Dietary flavonoids and the risk of lung cancer and other malignant neoplasms. Am J Epidemiol 146, 223–230.

    Article  CAS  Google Scholar 

  • Lazebnik YA, Kaufmann SH, Desnoyers S, Poirier GG, and Earnshaw WC (1994) Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE. Nature 371, 346–347.

    Article  CAS  Google Scholar 

  • Martindale JL and Holbrook NJ (2002) Cellular response to oxidative stress: signaling for suicide and survival. J Cell Physiol 192, 1–15.

    Article  CAS  Google Scholar 

  • Miyoshi N, Naniwa K, Yamada T, Osawa T, and Nakamura Y (2007) Dietary flavonoid apigenin is a potential inducer of intracellular oxidative stress: the role in the interruptive apoptotic signal. Arch Biochem Biophys 466, 274–282.

    Article  CAS  Google Scholar 

  • Persons DL, Yazlovitskaya EM, and Pelling JC (2000) Effect of extracellular signal-regulated kinase on p53 accumulation in response to cisplatin. J Biol Chem 275, 35778–35785.

    Article  CAS  Google Scholar 

  • Pietta PG (2000) Flavonoids as antioxidants. J Nat Prod 63, 1035–1042.

    Article  CAS  Google Scholar 

  • Prasad S, Phromnoi K, Yadav VR, Chaturvedi MM, and Aggarwal BB (2010) Targeting inflammatory pathways by flavonoids for prevention and treatment of cancer. Planta Med 76, 1044–1063.

    Article  CAS  Google Scholar 

  • Pumiglia KM and Decker SJ (1997) Cell cycle arrest mediated by the MEK/mitogen-activated protein kinase pathway. Proc Natl Acad Sci USA 94, 448–452.

    Article  CAS  Google Scholar 

  • Riedl SJ and Salvesen GS (2007) The apoptosome: signalling platform of cell death. Nat Rev Mol Cell Biol 8, 405–413.

    Article  CAS  Google Scholar 

  • Shin SY, Kim CG, Kim SH, Kim YS, Lim Y, and Lee YH (2010) Chlorpromazine activates p21Waf1/Cip1 gene transcription via early growth response-1 (Egr-1) in C6 glioma cells. Exp Mol Med 42, 395–405.

    Article  CAS  Google Scholar 

  • Shin SY, Kim CG, Lim Y, and Lee YH (2011) The ETS family transcription factor ELK-1 regulates induction of the cell cycle-regulatory gene p21(Waf1/Cip1) and the BAX gene in sodium arsenite-exposed human keratinocyte HaCaT cells. J Biol Chem 286, 26860–26872.

    Article  CAS  Google Scholar 

  • Shin SY, Kim JH, Lee JH, Lim Y, and Lee YH (2012) 2′-Hydroxyflavanone induces apoptosis through Egr-1 involving expression of Bax, p21, and NAG-1 in colon cancer cells. Mol Nutr Food Res 56, 761–774.

    Article  CAS  Google Scholar 

  • Singh RP and Agarwal R (2006) Natural flavonoids targeting deregulated cell cycle progression in cancer cells. Curr Drug Targets 7, 345–354.

    Article  CAS  Google Scholar 

  • Tu Y, Wu W, Wu T, Cao Z, Wilkins R, Toh BH et al. (2007) Antiproliferative autoantigen CDA1 transcriptionally up-regulates p21(Waf1/Cip1) by activating p53 and MEK/ERK1/2 MAPK pathways. J Biol Chem 282, 11722–11731.

    Article  CAS  Google Scholar 

  • Vousden KH and Lane DP (2007) p53 in health and disease. Nat Rev Mol Cell Biol 8, 275–283.

    Article  CAS  Google Scholar 

  • Wang IK, Lin-Shiau SY, and Lin JK (1999) Induction of apoptosis by apigenin and related flavonoids through cytochrome c release and activation of caspase-9 and caspase-3 in leukaemia HL-60 cells. Eur J Cancer 35, 1517–1525.

    Article  CAS  Google Scholar 

  • Wu GS (2004) The functional interactions between the p53 and MAPK signaling pathways. Cancer Biol Ther 3, 156–161.

    CAS  Google Scholar 

  • Xia Z, Dickens M, Raingeaud J, Davis RJ, and Greenberg ME (1995) Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270, 1326–1331.

    Article  CAS  Google Scholar 

  • Yang ZY, Perkins ND, Ohno T, Nabel EG, and Nabel GJ (1995) The p21 cyclin-dependent kinase inhibitor suppresses tumorigenicity in vivo. Nat Med 1, 1052–1056.

    Article  CAS  Google Scholar 

  • Yao LH, Jiang YM, Shi J, Tomas-Barberan FA, Datta N, Singanusong R et al. (2004) Flavonoids in food and their health benefits. Plant Foods Hum Nutr 59, 113–122.

    Article  CAS  Google Scholar 

  • Yu SW, Andrabi SA, Wang H, Kim NS, Poirier GG, Dawson TM et al. (2006) Apoptosis-inducing factor mediates poly(ADP-ribose) (PAR) polymer-induced cell death. Proc Natl Acad Sci USA 103, 18314–18319.

    Article  CAS  Google Scholar 

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Correspondence to Young Han Lee.

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Shin, S.Y., Lee, Y.H. 3-Hydroxyflavanone induces apoptosis in HeLa cells. J Korean Soc Appl Biol Chem 56, 113–116 (2013). https://doi.org/10.1007/s13765-012-2234-y

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