Browse > Article

Kaempferol induced the apoptosis via cell cycle arrest in human breast cancer MDA-MB-453 cells  

Choi, Eun-Jeong (Cancer Research Institute, The Catholic University of Korea)
Ahn, Woong-Shick (Cancer Research Institute, The Catholic University of Korea)
Publication Information
Nutrition Research and Practice / v.2, no.4, 2008 , pp. 322-325 More about this Journal
Abstract
The aim of present study was to investigate the effects of kaempferol on cellular proliferation and cell cycle arrest and explore the mechanism for these effects in human breast carcinoma MDA-MB-453 cells. Cells were treated with kaempferol at various concentrations (ranging from 1 to $200\;{\mu}M$) for 24 and 48 hrs. Kaempferol significantly inhibited cancer cell growth in cells exposed to 50 and $10\;{\mu}M$ of kaempferol and incubated for 24 and 48 hrs, respectively. Exposure to kaempferol resulted in cell cycle arrest at the G2/M phase. Of the G2/M-phase related proteins, kaempferol down-regulated CDK1 and cyclin A and B in cells exposed to kaempferol. In addition, small DNA fragments at the sub-G0 phase were increased by up to 23.12 and 31.90% at 10 and $50\;{\mu}M$ incubated for 24 and 48 hrs, respectively. The kaempferol-induced apoptosis was associated with the up-regulation of p53. In addition, the phosphorylation of p53 at the Ser-15 residue was observed with kaempferol. Kaempferol inhibits cell proliferation by disrupting the cell cycle, which is strongly associated with the induction of arrest at G2/M phase and may induce apoptosis via p53 phosphorylation in human breast carcinoma MDA-MB-453 cells.
Keywords
Apoptosis; cell cycle arrest; kaempferol; p53; human breast carcinoma MDA-MB-453 cells;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Bestwick CS, Milne L & Duthie SJ (2007). Kaempferol induced inhibition of HL-60 cell growth results from a heterogeneous response, dominated by cell cycle alterations. Chem Biol Interact 170:76-85   DOI   ScienceOn
2 Casagrande F & Darbon JM (2001). Effects of structurally related flavonoids on cell cycle progression of human melanoma cells: regulation of cyclin-dependent kinases CDK2 and CDK1. Biochem Pharmacol 61:1205-1215   DOI   ScienceOn
3 de Vries JH, Hollman PC, Meyboom S, Buysman MN, Zock PL, van Staveren WA & Katan MB (1998). Plasma concentrations and urinary excretion of the antioxidant flavonols quercetin and kaempferol as biomarkers for dietary intake. Am J Clin Nutr 68:60-65   DOI
4 Galati G & O'Brien PJ (2004). Potential toxicity of flavonoids and other dietary phenolics: significance for their chemopreventive and anticancer properties. Free Radic Biol Med 37:287-303   DOI   ScienceOn
5 Ito K, Nakazato T, Yamato K, Miyakawa Y, Yamada T, Hozumi N, Segawa K, Ikeda Y & Kizaki M (2004). Induction of apoptosis in leukemic cells by homovanillic acid derivative, capsaicin, through oxidative stress: implication of phosphorylation of p53 at Ser-15 residue by reactive oxygen species. Cancer Res 64:1071-1078   DOI   ScienceOn
6 Jessus C & Beach D (1992). Oscillation of MPF is accompanied by periodic association between cdc25 and cdc2-cyclin B. Cell 68:323-332   DOI   ScienceOn
7 Prouillet C, Mazière JC, Mazière C, Wattel A, Brazier M & Kamel S (2004). Stimulatory effect of naturally occurring flavonols quercetin and kaempferol on alkaline phosphatase activity in MG-63 human osteoblasts through ERK and estrogen receptor pathway. Biochem Pharmacol 67:1307-1313   DOI   ScienceOn
8 Ross JA & Kasum CM (2002). Dietary flavonoids: bioavailability, metabolic effects, and safety. Annu Rev Nutr 22:19-34   DOI   ScienceOn
9 Zhang Z, Li M, Rayburn ER, Hill DL, Zhang R & Wang H (2005). Oncogenes as novel targets for cancer therapy (part IV): regulators of the cell cycle and apoptosis. Am J Pharmacogenomics 5:397-407   DOI   ScienceOn
10 Nguyen TT, Tran E, Ong CK, Lee SK, Do PT, Huynh TT, Nguyen TH, Lee JJ, Tan Y, Ong CS & Huynh H (2003b). Kaempferolinduced growth inhibition and apoptosis in A549 lung cancer cells is mediated by activation of MEK-MAPK. J Cell Physiol 197:110-121   DOI   ScienceOn
11 Zhang Q, Zhao XH & Wang ZJ (2008). Flavones and flavonols exert cytotoxic effects on a human oesophageal adenocarcinoma cell line (OE33) by causing G2/M arrest and inducing apoptosis. Food Chem Toxicol 46:2042-2053   DOI   ScienceOn
12 Chen D, Daniel KG, Chen MS, Kuhn DJ, Landis-Piwowar KR & Dou QP (2005). Dietary flavonoids as proteasome inhibitors and apoptosis inducers in human leukemia cells. Biochem Pharmacol 69:1421-1432   DOI   ScienceOn
13 Leung HW, Lin CJ, Hour MJ, Yang WH, Wang MY & Lee HZ (2007). Kaempferol induces apoptosis in human lung non-small carcinoma cells accompanied by an induction of antioxidant enzymes. Food Chem Toxicol 45:2005-2013   DOI
14 Fesik SW (2005). Promoting apoptosis as a strategy for cancer drug discovery. Nat Rev Cancer 5:876-885   DOI   ScienceOn
15 Knowles LM, Zigrossi DA, Tauber RA, Hightower C & Milner JA (2000). Flavonoids suppress androgen-independent human prostate tumor proliferation. Nutr Cancer 38:116-122   DOI   ScienceOn
16 Hung H (2004). Inhibition of estrogen receptor alpha expression and function in MCF-7 cells by kaempferol. J Cell Physiol 198:197-208   DOI   ScienceOn
17 Miean KH & Mohamed S (2001). Flavonoid (myricetin, quercetin, kaempferol, luteolin, and apigenin) content of edible tropical plants. J Agric Food Chem 49:3106-3112   DOI   ScienceOn
18 Yoshida T, Konishi M, Horinaka M, Yasuda T, Goda AE, Taniguchi H, Yano K, Wakada M & Sakai T (2008). Kaempferol sensitizes colon cancer cells to TRAIL-induced apoptosis. Biochem Biophys Res Commun 375:129-133   DOI   ScienceOn
19 Marfak A, Trouillas P, Allais DP, Champavier Y, Calliste CA & Duroux JL (2003). Radiolysis of kaempferol in water/methanol mixtures. Evaluation of antioxidant activity of kaempferol and products formed. J Agric Food Chem 51:1270-1277   DOI
20 Ren W, Qiao Z, Wang H, Zhu L & Zhang L (2003). Flavonoids: promising anticancer agents. Med Res Rev 23:519-534   DOI   ScienceOn
21 Park JS, Rho HS, Kim DH & Chang IS (2006). Enzymatic preparation of kaempferol from green tea seed and its antioxidant activity. J Agric Food Chem 54:2951-2956   DOI   ScienceOn
22 Morla AO, Draetta G, Beach D & Wang JY (1989). Reversible tyrosine phosphorylation of cdc2: dephosphorylation accompanies activation during entry into mitosis. Cell 58:193-203   DOI
23 Nguyen TT, Tran E, Ong CK, Lee SK, Do PT, Huynh TT, Nguyen TH, Lee JJ, Tan Y, Ong CS & Huynh H (2003a). Kaempferolinduced growth inhibition and apoptosis in A549 lung cancer cells is mediated by activation of MEK-MAPK. J Cell Physiol 197:110-121   DOI
24 Sun SY, Hail N & Lotan R (2004). Apoptosis as a novel target for cancer chemoprevention. J Natl Cancer Inst 96:2662-2672
25 Jiang C, Hu H, Malewicz B, Wang Z & Lü J (2004). Selenite-induced p53 Ser-15 phosphorylation and caspase-mediated apoptosis in LNCaP human prostate cancer cells. Mol Cancer Ther 3:877-884
26 Kuo PC, Liu HF & Chao JI (2004). Survivin and p53 modulate quercetin-induced cell growth inhibition and apoptosis in human lung carcinoma cells. J Biol Chem 279:55875-55885   DOI
27 Guimaraes DP & Hainaut P (2002). TP53: a key gene in human cancer. Biochimie 84:83-93   DOI   ScienceOn
28 Mota I, Wong D & Sadun EH (1968). Mouse homocytotropic antibodies. I. Specific differentiation between mouse 7S gamma 1 and mouse reagin-like antibodies. Life Sci 7:1289-1293   DOI