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Planta Med 2012; 78(09): 899-902
DOI: 10.1055/s-0031-1298464
Biological and Pharmacological Activity
Letters
Georg Thieme Verlag KG Stuttgart · New York

The Effect of Silymarin on Telomerase Activity in the Human Leukemia Cell Line K562

Zohreh Faezizadeh
1   Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
,
Seyed Ali Reza Mesbah-Namin
1   Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
,
Abdolamir Allameh
1   Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
› Author Affiliations
Further Information

Publication History

received 05 February 2012
revised 15 March 2012

accepted 28 March 2012

Publication Date:
24 April 2012 (online)

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Abstract

Telomerase has been proposed as a novel and potentially selective target in cancer therapy. Silymarin, which is a standardized mixture of flavonolignans from the medical plant Silybum marianum, has potent effects against various types of cancer cells, but its effect on telomerase activity in the human leukemia cell line K562 has not been investigated. The aim of this study was to examine the mechanism of silymarin-induced apoptosis in K562 cells, with particular emphasis on its effect on telomerase activity. The antiproliferation effect of silymarin on K562 cells was evaluated by the MTT assay. To measure apoptosis, Hoechst 33342 staining and flow cytometry were used. The telomerase activity was determined using the telomeric repeat amplification protocol (TRAP)-ELISA assay. The treatment of the K562 cells with silymarin resulted in a significant inhibition of cell growth and telomerase activity. Also, a positive correlation was found between telomerase inhibition and induction of apoptosis in silymarin-treated K562 cells. These results suggest a novel mechanism in the anticancer activity of silymarin in human leukemia K562 cells and may provide a basis for future development of anti-telomerase therapies.

Key words

K562 - silymarin - telomerase activity - apoptosis - Silybum marianum - Asteraceae
 

  • References

  • 1 Tian X, Chen B, Liu X. Telomere and telomerase as targets for cancer therapy. Appl Biochem Biotechnol 2010; 160: 1460-1472
    CrossrefPubMedGoogle Scholar
  • 2 Cheung AL, Deng W. Telomere dysfunction, genome instability and cancer. Front Biosci 2008; 1: 2075-2090
    PubMedGoogle Scholar
  • 3 Harley CB. Telomerase and cancer therapeutics. Nat Rev Cancer 2008; 8: 167-179
    CrossrefPubMedGoogle Scholar
  • 4 Zimmermann S, Martens UM. Telomeres and telomerase as targets for cancer therapy. Cell Mol Life Sci 2007; 64: 906-921
    CrossrefPubMedGoogle Scholar
  • 5 Huang ST, Wang CY, Yang RC, Chu CJ, Wu HT, Pang JH. Wogonin, an active compound in Scutellariabai calensis, induces apoptosis and reduces telomerase activity in the HL-60 leukemia cells. Phytomedicine 2010; 138: 1747-1754
    PubMedGoogle Scholar
  • 6 Ji ZN, Ye WC, Liu GQ, Huang Y. Inhibition of telomerase activity and bcl-2 expression in berbamine-induced apoptosis in HL-60 cells. Planta Med 2002; 68: 596-600
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Wang X, Hao MW, Dong K, Lin F, Ren JH, Zhang HZ. Apoptosis induction effects of EGCG in laryngeal squamous cell carcinoma cells through telomerase repression. Arch Pharm Res 2009; 3: 1263-1269
    PubMedGoogle Scholar
  • 8 Lin SC, Li WC, Shih JW, Hong KF, Pan YR, Lin JJ. The tea polyphenols EGCG and EGC repress mRNA expression of human telomerase reverse transcriptase (hTERT) in carcinoma cells. Cancer Lett 2006; 236: 80-88
    CrossrefPubMedGoogle Scholar
  • 9 Ramachandran C, Fonseca HB, Jhabvala P, Escalon EA, Melnick SJ. Curcumin inhibits telomerase activity through human telomerase reverse transcritpase in MCF-7 breast cancer cell line. Cancer Lett 2002; 184: 1-6
    CrossrefPubMedGoogle Scholar
  • 10 Moon DO, Kim MO, Choi YH, Lee HG, Kim ND, Kim GY. Gossypol suppresses telomerase activity in human leukemia cells via regulating hTERT. FEBS Lett 2008; 582: 3367-3373
    CrossrefPubMedGoogle Scholar
  • 11 Moon DO, Kim MO, Lee JD, Choi YH, Kim GY. Butein suppresses c-Myc-dependent transcription and Akt-dependent phosphorylation of hTERT in human leukemia cells. Cancer Lett 2009; 286: 172-179
    CrossrefPubMedGoogle Scholar
  • 12 Park SE, Park C, Kim SH, Hossain MA, Kim MY, Chung HY, Son WS, Kim GY, Choi YH, Kim ND. Korean red ginseng extract induces apoptosis and decreases telomerase activity in human leukemia cells. J Ethnopharmacol 2009; 121: 304-312
    CrossrefPubMedGoogle Scholar
  • 13 Park DI, Lee JH, Moon SK, Kim CH, Lee YT, Cheong J, Choi BT, Choi YH. Induction of apoptosis and inhibition of telomerase activity by aqueous extract from Platycodon grandiflorum in human lung carcinoma cells. Pharmacol Res 2005; 51: 437-443
    CrossrefPubMedGoogle Scholar
  • 14 Zhong X, Zhu Y, Lu Q, Zhang J, Ge Z, Zheng S. Silymarin causes caspases activation and apoptosis in K562 leukemia cells through inactivation of Akt pathway. Toxicology 2006; 227: 211-216
    CrossrefPubMedGoogle Scholar
  • 15 Katiyar SK, Roy AM, Baliga MS. Silymarin induces apoptosis primarily through a P53-dependent pathway involving Bcl-2/Bax, cytochrome C release, and caspase activation. Mol Cancer Ther 2005; 4: 207-216
    CrossrefPubMedGoogle Scholar
  • 16 Mansour HH, Hafez HF, Fahym NM. Silymarin modulate cisplatin-induced oxidative stress and hepatotoxicity in rats. J Biochem Mol Biol 2006; 39: 656-661
    CrossrefPubMedGoogle Scholar
  • 17 Matsuda T, Ferreri K, Todorov I, Kuroda Y, Smith CV, Kandeel F, Mullen Y. Silymarin protects pancreatic betacells against cytokine-mediated toxicity: implication of c-Jun NH2-terminal kinase and janus kinase/signal transducer and activator of transcription pathways. Endocrinology 2005; 146: 175-185
    PubMedGoogle Scholar
  • 18 Kiruthiga PV, Shafreen RB, Pandian SK, Devi KP. Silymarin protection against major reactive oxygen species released by environmental toxins: exogenous H2O2 exposure in erythrocytes. Basic Clin Pharmacol Toxicol 2007; 100: 414-419
    CrossrefPubMedGoogle Scholar
  • 19 Ramasamy K, Agarwal R. Multitargeted therapy of cancer by silymarin. Cancer Lett 2008; 269: 352-362
    CrossrefPubMedGoogle Scholar
  • 20 Tyagi A, Bhatia N, Condon MS, Bosland MC, Agarwal C, Agarwal R. Antiproliferative and apoptotic effects of silibinin in rat prostate cancer cells. Prostate 2002; 53: 211-217
    CrossrefPubMedGoogle Scholar
  • 21 Ramakrishnan L, Muzio L, Elinos-Baz CM, Jagan S, Augustine TA, Kamaraj S, Anandakumar P, Devaki T. Silymarin inhibited proliferation and induced apoptosis in hepatic cancer cells. Cell Prolif 2009; 42: 229-240
    CrossrefPubMedGoogle Scholar
  • 22 Deep G, Agarwal R. Chemopreventive efficacy of silymarin in skin and prostate cancer. Integr Cancer Ther 2007; 6: 130-145
    CrossrefPubMedGoogle Scholar
  • 23 Tyagi A, Raina K, Singh RP, Gu M, Agarwal C, Harrison G, Glode LM, Agarwal R. Chemopreventive effects of silymarin and silibinin on N-butyl-N-(4-hydroxybutyl) nitrosamine induced urinary bladder carcinogenesis in male ICR mice. Mol Cancer Ther 2007; 6: 3248-3255
    CrossrefPubMedGoogle Scholar
  • 24 Wen Z, Dumas TE, Schrieber SJ, Hawke RL, Fried MW, Smith PC. Pharmacokinetics and metabolic profile of free, conjugated, and total silymarin flavonolignans in human plasma after oral administration of milk thistle extract. Drug Metab Dispos 2008; 36: 65-72
    PubMedGoogle Scholar
  • 25 Mor-Tzuntz R, Uziel O, Shpilberg O, Lahav J, Raanani P, Bakhanashvili M, Rabizadeh E, Zimra Y, Lahav M, Granot G. Effect of imatinib on the signal transduction cascade regulating telomerase activity in K562 (BCR-ABL-positive) cells sensitive and resistant to imatinib. Exp Hematol 2010; 38: 27-37
    CrossrefPubMedGoogle Scholar
  • 26 Chai JH, Zhang Y, Tan WH, Chng WJ, Li B, Wang X. Regulation of hTERT by BCR-ABL at multiple levels in K562 cells. BMC Cancer 2011; 11: 512-528
    CrossrefPubMedGoogle Scholar
  • 27 Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Meth 1983; 65: 55-63
    CrossrefPubMedGoogle Scholar
  • 28 Barford MM. Rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248-254
    CrossrefPubMedGoogle Scholar