DOI QR코드

DOI QR Code

Curcumin and Silibinin Inhibit Telomerase Expression in T47D Human Breast Cancer Cells

  • Nasiri, Marzieh (Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, School of Medicine, Tabriz University of Medical Sciences) ;
  • Zarghami, Nosratollah (Tuberculosis and Lung Research Center, Tabriz University of Medical Sciences) ;
  • Koshki, Kazem Nejati (Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, School of Medicine, Tabriz University of Medical Sciences) ;
  • Mollazadeh, Mahdieh (Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, School of Medicine, Tabriz University of Medical Sciences) ;
  • Moghaddam, Mohammad Pourhassan (Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, School of Medicine, Tabriz University of Medical Sciences) ;
  • Yamchi, Mohammad Rahmati (Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, School of Medicine, Tabriz University of Medical Sciences) ;
  • Esfahlan, Rana Jahanban (Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, School of Medicine, Tabriz University of Medical Sciences) ;
  • Barkhordari, Amin (Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, School of Medicine, Tabriz University of Medical Sciences) ;
  • Alibakhshi, Abbas (Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, School of Medicine, Tabriz University of Medical Sciences)
  • Published : 2013.06.30

Abstract

Background: Telomerase has been considered as an attractive molecular target for breast cancer therapy. The main objective of this work is to assess the inhibitory effects of silibinin and curcumin, two herbal substances, on telomerase gene expression in breast cancer cells. Materials and Methods: For determination of cell viability tetrazolium-based assays were conducted after 24, 48, and 72 h exposure times and expression of human telomerase reverse transcriptase gene was measured with real-time PCR. Results: Each compound exerted cytotoxic effects on T47D cells and inhibited telomerase gene expression, both in a time-and dose-dependent manner. The mixture of curcumin and silibinin showed relatively more inhibitory effect on growth of T47D cells and hTERT gene expression as compared with either agent alone. Conclusions: These findings suggest that cell viability along with hTERT gene expression in breast cancer cells could be reduced by curcumin and silibinin.

Keywords

Curcumin;silibinin;breast cancer;telomerase

References

  1. Choudhuri T, Pal S, Agwarwal ML, Das T, Sa G (2002). Curcumin induces apoptosis in human breast cancer cells through p53-dependent Bax induction. FEBS Lett, 512, 334-40. https://doi.org/10.1016/S0014-5793(02)02292-5
  2. Jemal A, Siegel R, Xu J, Ward E (2010). Cancer statistics. CA Cancer J Clin, 60, 277-300. https://doi.org/10.3322/caac.20073
  3. Ju Z, Rudolph KL (2006). Telomeres and telomerase in cancer stem cells. Eur J Cancer, 42, 1197-203. https://doi.org/10.1016/j.ejca.2006.01.040
  4. Kaur M, Velmurugan B, Tyagi A, et al (2009). Silibinin suppresses growth and induces apoptotic death of human colorectal carcinoma LoVo cells in culture and tumor xenograft. Mol Cancer Ther, 8, 2366-74. https://doi.org/10.1158/1535-7163.MCT-09-0304
  5. Kim S, Choi JH, Lim HI, et al (2009). Silibinin prevents TPA-induced MMP-9 expression and VEGF secretion by inactivation of the Raf/MEK/ERK pathway in MCF-7 human breast cancer cells. Phytomedicine, 16, 573-80. https://doi.org/10.1016/j.phymed.2008.11.006
  6. Bundred NJ (2001). Prognostic and predictive factors in breast cancer. Cancer Treat Rev, 27, 137-42. https://doi.org/10.1053/ctrv.2000.0207
  7. Chakravarti N, Kadara H, Yoon DJ, et al (2010). Differential inhibition of protein translation machinery by curcumin in normal, immortalized, and malignant oral epithelial cells. Cancer Prev Res (Phila), 3, 331-8. https://doi.org/10.1158/1940-6207.CAPR-09-0076
  8. Lin CJ, Sukarieh R, Pelletier J (2009). Silibinin inhibits translation initiation: implications for anticancer therapy. Mol Cancer Ther, 8, 1606-12. https://doi.org/10.1158/1535-7163.MCT-08-1152
  9. Massard C, Zermati Y, Pauleau AL, et al (2006). hTERT: a novel endogenous inhibitor of the mitochondrial cell death pathway. Oncogene, 25, 4505-14. https://doi.org/10.1038/sj.onc.1209487
  10. Mukherjee Nee Chakraborty S, Ghosh U, Bhattacharyya NP, Dey S, Roy M (2007). Curcumin-induced apoptosis in human leukemia cell HL-60 is associated with inhibition of telomerase activity. Mol Cell Biochem, 297, 31-9. https://doi.org/10.1007/s11010-006-9319-z
  11. Nakamura M, Masutomi K, Kyo S, et al (2005). Efficient inhibition of human telomerase reverse transcriptase expression by RNA interference sensitizes cancer cells to ionizing radiation and chemotherapy. Hum Gene Ther, 16, 859-68. https://doi.org/10.1089/hum.2005.16.859
  12. Ramachandran C, You W (1999). Differential sensitivity of human mammary epithelial and breast carcinoma cell lines to curcumin. Breast Cancer Res Treat, 54, 269-78. https://doi.org/10.1023/A:1006170224414
  13. Ramachandran C, Fonseca HB, Jhabvala P, Escalon EA, Melnick SJ (2002). Curcumin inhibits telomerase activity through human telomerase reverse transcritpase in MCF-7 breast cancer cell line. Cancer Lett, 184, 1-6. https://doi.org/10.1016/S0304-3835(02)00192-1
  14. Sa G, Das T (1997). Anti cancer effects of curcumin: cycle of life and death. Cell Div, 3, 14.
  15. Shay JW, Gazdar AF (1997). Telomerase in the early detection of cancer. J Clin Pathol, 50, 106-9. https://doi.org/10.1136/jcp.50.2.106
  16. Subramaniam D, Ponnurangam S, Ramamoorthy P, et al (2012). Curcumin induces cell death in esophageal cancer cells through modulating Notch signaling. PLoS One, 7, 30590. https://doi.org/10.1371/journal.pone.0030590
  17. Syng-Ai C, Kumari AL, Khar A (2004). Effect of curcumin on normal and tumor cells: role of glutathione and bcl-2. Mol Cancer Ther, 3, 1101-18.
  18. Thelen P, Wuttke W, Jarry H, Grzmil M, Ringert RH (2004). Inhibition of telomerase activity and secretion of prostate specific antigen by silibinin in prostate cancer cells. J Urol, 171, 1934-8. https://doi.org/10.1097/01.ju.0000121329.37206.1b
  19. Tyagi AK, Agarwal C, Chan DC, Agarwal R (2004). Synergistic anti-cancer effects of silibinin with conventional cytotoxic agents doxorubicin, cisplatin and carboplatin against human breast carcinoma MCF-7 and MDA-MB468 cells. Oncol Rep, 11, 493-9.
  20. Wang HJ, Jiang YY, Wei XF, et al (2010). Silibinin induces protective superoxide generation in human breast cancer MCF-7 cells. Free Radic Res, 44, 90-100. https://doi.org/10.3109/10715760903300717
  21. Wang L, Soria JC, Kemp BL, et al (2002). hTERT expression is a prognostic factor of survival in patients with stage I nonsmall cell lung cancer. Clin Cancer Res, 8, 2883-9.
  22. Watson JL, Greenshields A, Hill R, et al (2010). Curcumininduced apoptosis in ovarian carcinoma cells is p53-independent and involves p38 mitogen-activated protein kinase activation and downregulation of Bcl-2 and survivin expression and Akt signaling. Mol Carcinog, 49, 13-24.
  23. Wilken R, Veena MS, Wang MB, Srivatsan ES (2011). Curcumin: A review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma. Mol Cancer, 10, 12. https://doi.org/10.1186/1476-4598-10-12
  24. Yeo M, Rha SY, Jeung HC, et al (2005). Attenuation of telomerase activity by hammerhead ribozyme targeting human telomerase RNA induces growth retardation and apoptosis in human breast tumor cells. Int J Cancer, 114, 484-9. https://doi.org/10.1002/ijc.20720
  25. Zou L, Zhang P, Luo C, Tu Z (2006). Mad1 suppresses bladder cancer cell proliferation by inhibiting human telomerase reverse transcriptase transcription and telomerase activity. Urology, 67, 1335-40. https://doi.org/10.1016/j.urology.2005.12.029

Cited by

  1. PAMAM Dendrimers Augment Inhibitory Effects of Curcumin on Cancer Cell Proliferation: Possible Inhibition of Telomerase vol.14, pp.11, 2013, https://doi.org/10.7314/APJCP.2013.14.11.6925
  2. Inhibitory Effects of β-Cyclodextrin-Helenalin Complexes on H-TERT Gene Expression in the T47D Breast Cancer Cell Line - Results of Real Time Quantitative PCR vol.14, pp.11, 2013, https://doi.org/10.7314/APJCP.2013.14.11.6949
  3. Curcumin and its Analogues (PGV-0 and PGV-1) Enhance Sensitivity of Resistant MCF-7 Cells to Doxorubicin through Inhibition of HER2 and NF-kB Activation vol.15, pp.1, 2014, https://doi.org/10.7314/APJCP.2014.15.1.179
  4. Molecular Target Therapy of AKT and NF-kB Signaling Pathways and Multidrug Resistance by Specific Cell Penetrating Inhibitor Peptides in HL-60 Cells vol.15, pp.10, 2014, https://doi.org/10.7314/APJCP.2014.15.10.4353
  5. Novel DOX-MTX Nanoparticles Improve Oral SCC Clinical Outcome by Down Regulation of Lymph Dissemination Factor VEGF-C Expression in vivo: Oral and IV Modalities vol.15, pp.15, 2014, https://doi.org/10.7314/APJCP.2014.15.15.6227
  6. Trichostatin A-induced Apoptosis is Mediated by Krüppel-like Factor 4 in Ovarian and Lung Cancer vol.15, pp.16, 2014, https://doi.org/10.7314/APJCP.2014.15.16.6581
  7. Silibinin Inhibits Proliferation, Induces Apoptosis and Causes Cell Cycle Arrest in Human Gastric Cancer MGC803 Cells Via STAT3 Pathway Inhibition vol.15, pp.16, 2014, https://doi.org/10.7314/APJCP.2014.15.16.6791
  8. DOX-MTX-NPs Augment p53 mRNA Expression in OSCC Model in Rat: Effects of IV and Oral Routes vol.15, pp.19, 2014, https://doi.org/10.7314/APJCP.2014.15.19.8377
  9. Induction of MicroRNA-9 Mediates Cytotoxicity of Curcumin Against SKOV3 Ovarian Cancer Cells vol.15, pp.8, 2014, https://doi.org/10.7314/APJCP.2014.15.8.3363
  10. Fenugreek extract diosgenin and pure diosgenin inhibit the hTERT gene expression in A549 lung cancer cell line vol.41, pp.9, 2014, https://doi.org/10.1007/s11033-014-3505-y
  11. Diterpenoid C of Radix Curcumae: An inhibitor of proliferation and inducer of apoptosis in human colon adenocarcinoma cells acting via inhibiting MAPK signaling pathway vol.52, pp.9, 2014, https://doi.org/10.3109/13880209.2013.879907
  12. Oral and IV Dosages of Doxorubicin-Methotrexate loaded-Nanoparticles Inhibit Progression of Oral Cancer by Down-Regulation of Matrix Methaloproteinase 2 Expression in Vivo vol.15, pp.24, 2015, https://doi.org/10.7314/APJCP.2014.15.24.10705
  13. Anti-Proliferative Effects of Hesa-A on Human Cancer Cells with Different Metastatic Potential vol.16, pp.16, 2015, https://doi.org/10.7314/APJCP.2015.16.16.6963
  14. Silibilin-Induces Apoptosis in Breast Cancer Cells by Modulating p53, p21, Bak and Bcl-xl Pathways vol.16, pp.5, 2015, https://doi.org/10.7314/APJCP.2015.16.5.2087
  15. Deactivation of Telomerase Enzyme and Telomere Destabilization by Natural Products: a Potential Target for Cancer Green Therapy vol.16, pp.18, 2016, https://doi.org/10.7314/APJCP.2015.16.18.8671
  16. Regulation of the Telomerase Reverse Transcriptase Subunit through Epigenetic Mechanisms vol.7, pp.1664-8021, 2016, https://doi.org/10.3389/fgene.2016.00083
  17. Bringing Curcumin to the Clinic in Cancer Prevention: a Review of Strategies to Enhance Bioavailability and Efficacy vol.19, pp.1, 2017, https://doi.org/10.1208/s12248-016-0003-2
  18. Emerging Importance of Phytochemicals in Regulation of Stem Cells Fate via Signaling Pathways vol.31, pp.11, 2017, https://doi.org/10.1002/ptr.5908
  19. Curcumin: the spicy modulator of breast carcinogenesis vol.36, pp.1, 2017, https://doi.org/10.1186/s13046-017-0566-5
  20. New insights into antidiabetic drugs: Possible applications in cancer treatment vol.90, pp.6, 2017, https://doi.org/10.1111/cbdd.13013
  21. Nano-encapsulated metformin-curcumin in PLGA/PEG inhibits synergistically growth and hTERT gene expression in human breast cancer cells pp.2169-141X, 2017, https://doi.org/10.1080/21691401.2017.1347879
  22. Telomerase Inhibitors from Natural Products and Their Anticancer Potential vol.19, pp.1, 2017, https://doi.org/10.3390/ijms19010013
  23. gene expression in mouse B16F10 melanoma tumour model pp.2169-141X, 2018, https://doi.org/10.1080/21691401.2018.1452021