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HOW DOES QUERCETIN AND TAMOXIFEN AFFECT THE APOPTOSIS OF COLON CANCER CELLS?

Year 2015, Volume: 37 Issue: 2, 14 - 20, 25.12.2015

Abstract

KOLON KANSER HÜCRELERİNİN APOPTOZUNU KERSETİN VE TAMOKSİFEN NASIL ETKİLER?

Özet: Diyetle alınan çeşitli sebze ve meyvelerde bulunan bileşiklerin kanser tedavisine yardımcı olabileceği bilinmektedir. Polifenolik bir bileşik olan kersetinin de bazı kanserlerde çeşitli moleküller üzerinden etkili olabildiği hakkında mevcut araştırmalar vardır. Ancak etki mekanizmalarının belirlenmesi için çalışmalar devam etmekte olup, tam olarak açıklığa kavuşmamıştır. Tamoksifen ise östrojen pozitif meme kanserinin tedavisinde kullanılan bir nonsteroid anti-östrojen ilaçtır. Zaman zaman meme kanseri dışında diğer bazı kanserlerde de kullanıldığı hakkında çeşitli bilgilere sahip olduğumuz tamoksifenin, kolon kanserinde de etkili olabileceğini düşünerek araştırmamızda kolon kanser hücrelerinde bu iki bileşenin apoptoz üzerine etkilerini incelemeyi amaçladık.  Kersetin ve tamoksifenin 24, 48 ve 72. saatlerde apoptotik indekse olan etkileri TUNEL metodu belirlendi. Kolon kanser hücrelerinde kersetin ve tamoksifenin çeşitli konsantrasyonlarda (25, 50 ve 100 µM) apoptotik indekse olan etkileri belirlendi. Bulgular: Apoptotik indeksin kersetin ve tamoksifen uygulanan gruplarda kontrol grubuna göre arttığı bulundu. Apoptotic index increased in groups that were administered quercetin and tamoxifen compared to control groups. Kolon adeno karsinomada kersetin ve tamoksifenin apoptozu indükleyerek kanser tedavisinde önemli bir rol oynayabileceğini bulunmuştur.

ANAHTAR KELİMELER: Apoptoz, CaCo-2, Kersetin, Kolon Kanseri, Tamoksifen

 

Abstarcat: It is a known fact that compounds found in various vegetables and fruits taken by diet may be of help in treating cancer. A polyphenolic compound, quercetin was reported to have a possible impact on some types of cancer through a variety of molecules. However, there are ongoing studies to prove the effect mechanisms and it has yet to be clarified. Tamoxifen is a non-steroidal anti-estrogen drug used in the treatment of estrogen-positive breast cancer. We already have some information regarding occasional use of tamoxifen in treatment of some cancers other than breast cancer, and thus we began investigating the effects of these two components on apoptosis in colon cancer cells in our study considering that it may also be effective in colon cancer. The effect of quercetin and tamoxifen on apoptotic index was evaluated by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method at the 24th, 48th, and 72nd hours. In colon cancer cells, the effects of various concentrations (25, 50, and 100 µM) of quercetin and tamoxifen on apoptotic index in colon cancer cells were established. Apoptotic index increased in groups that were administered quercetin and tamoxifen compared to control groups. The current study shows that quercetin and tamoxifen may play an important role in the treatment of cancer by inducing apoptosis in colon adenocarcinoma.

KEYWORD: Apoptosis, CaCo-2, Quercetin, Colon Cancer, Tamoxifen

References

  • Johnson, D.Y. Wadhwa, S. and Johnson, F.E. (2013). Colon and Rectum Carcinoma. In Patient Surveillance After Cancer Treatment: Springer. 179-183.
  • Konstantinopoulos, P. Kominea, A. Vandoros, G. Sykiotis, G. Andricopoulos, P. Varakis, I. Sotiropoulou-Bonikou, G. and Papavassiliou, A. (2003). Oestrogen receptor beta (ERβ) is abundantly expressed in normal colonic mucosa, but declines in colon adenocarcinoma paralleling the tumour's dedifferentiation. European Journal of Cancer 39:1251-1258.
  • Campbell-Thompson, M. Lynch, I.J. and Bhardwaj, B. (2001). Expression of estrogen receptor (ER) subtypes and ERbeta isoforms in colon cancer. Cancer Res 61:632-640.
  • Picariello, L. Fiorelli, G. Martineti, V. Tognarini, I. Pampaloni, B. Tonelli, F. and Brandi, M.L. (2002). Growth response of colon cancer cell lines to selective estrogen receptor modulators. Anticancer research 23:2419-2424.
  • Rajamanickam, S. and Agarwal, R. (2008). Natural products and colon cancer: current status and future prospects. Drug Dev Res 69:460-471.
  • van Erk, M.J. Roepman, P. van der Lende, T.R. Stierum, R.H. Aarts, J. van Bladeren, P.J. and van Ommen, B. (2005). Integrated assessment by multiple gene expression analysis anticancer–related cancer cells in vitro. European journal of nutrition 44:143-156. bioactivity on mechanisms in colon
  • Galluzzo, P. Martini, C. Bulzomi, P. Leone, S. Bolli, A. Pallottini, V. and Marino, M. (2009). Quercetin‐induced apoptotic cascade in cancer cells: Antioxidant versus estrogen receptor α‐ dependent mechanisms. Molecular nutrition & food research 53:699-708.
  • Gibellini, L. Pinti, M. Nasi, M. Montagna, J.P. De Biasi, S. Roat, E. Bertoncelli, L. Cooper, E.L. and Cossarizza, A. (2011). Quercetin and cancer Complementary and Alternative Medicine 2011. Evidence-Based
  • Bulzomi, P. Galluzzo, P. Bolli, A. Leone, S. Acconcia, F. and Marino, M. (2012). The pro‐ apoptotic effect of quercetin in cancer cell lines requires ERβ‐dependent signals. Journal of Cellular Physiology 227:1891-1898.
  • Kumar, R. Verma, V. Jain, A. Jain, R.K. Maikhuri, J.P. and Gupta, G. (2011). Synergistic chemoprotective mechanisms of dietary phytoestrogens in a select combination against prostate cancer. J Nutr Biochem 22:723-731.
  • Khalkhali-Ellis, Z. Kirschmann, D.A. Edwards, E.M. Rezaie- Thompson, M. Vasef, M.A. Gruman, L.M. Seftor, R.E. Norwood, L.E. and Hendrix, M.J. (2004). Regulating the Tumor Suppressor Gene Maspin in Breast Cancer Cells A Potential Mechanism for the Anticancer Properties of Tamoxifen. Clinical cancer research 10:449-454. Christian, A.L.
  • Petinari, L. Kohn, L.K. de Carvalho, J.E. and Genari, S.C. (2004). Cytotoxicity of tamoxifen in normal and tumoral cell lines and its ability to induce cellular transformation in vitro. Cell biology international 28:531-539.
  • Aldous, W.K. Marean, A.J. DeHart, M.J. Matej, L.A. and Moore, K.H. (1999). Effects of tamoxifen on telomerase activity in breast carcinoma cell lines. Cancer 85:1523-1529. 14. Cosan, D. Soyocak, A. Basaran, A. Degirmenci, I. and Güneş, H.V. (2009). The effects of resveratrol and tannic acid on apoptosis in colon adenocarcinoma cell line. Saudi Med J 30:191-195.
  • Kim, W.K. Bang, M.H. Kim, E.S. Kang, N.E. Jung, K.C. Cho, H.J. and Park, J.H. (2005). Quercetin decreases the expression of ErbB2 and ErbB3 proteins in HT-29 human colon cancer cells. J Nutr Biochem 16:155-162.
  • Shan, B.-E. Wang, M.-X. and Li, R.-q. (2009). Quercetin inhibit human SW480 colon cancer growth in association with inhibition of cyclin D1 and survivin expression through Wnt/β- catenin investigation 27:604-612. pathway. Cancer
  • Murtaza, I. Marra, G. Schlapbach, R. Patrignani, A. Künzli, M. Wagner, U. Sabates, J. and Dutt, A. (2006). A preliminary investigation demonstrating the effect of quercetin on the expression of genes related to cell‐cycle arrest, apoptosis and xenobiotic metabolism adenocarcinoma cells using DNA microarray. Biotechnology and applied biochemistry 45:29-36. CO115 colon‐
  • Kim, H.J. Kim, S.K. Kim, B.S. Lee, S.H. Park, Y.S. Park, B.K. Kim, S.J. Kim, J. Choi, C. Kim, J.S. et al. (2010). Apoptotic effect of quercetin on HT-29 colon cancer cells via the AMPK signaling pathway. J Agric Food Chem 58:8643-8650.
  • van der Woude, H. Gliszczyńska-Świgło, A. Struijs, K. Smeets, A. Alink, G.M. and Rietjens, I.M. (2003). Biphasic modulation of cell concentrations physiologically relevant in humans. Cancer letters 200:41-47. at
  • Ak, A. Başaran, A. Dikmen, M. Coşan, D.T. Değirmenci, İ. and Güneş, H.V. (2011). Evaluation of Effects of Quercetin (3, 3’, 4’, 5, 7-pentohidroxyflavon) on Apoptosis and Telomerase Enzyme Activity in MCF-7 and NIH-3T3 Tamoxifen. Balkan Medical Journal 28:293- 299. Compared with
  • Choi, J.A. Kim, J.Y. Lee, J.Y. Kang, C.M. Kwon, H.J. Yoo, Y.D. Kim, T.W. Lee, Y.S. and Lee, S.J. (2001). Induction of cell cycle arrest and apoptosis in human breast cancer cells by quercetin. Int J Oncol 19:837-844.
  • Nichenametla, S.N. Taruscio, T.G. Barney, D.L. and Exon, J.H. (2006). A review of the effects and mechanisms of polyphenolics in cancer. Critical reviews in food science and nutrition 46:161-183.
  • Rodgers, E.H. and Grant, M.H. (1998). The effect of the flavonoids, quercetin, myricetin and epicatechin on the growth and enzyme activities of MCF7 human breast cancer cells. Chemico-biological interactions 116:213-228.
  • Psahoulia, F.H. Drosopoulos, K.G. Doubravska, L. Andera, L. and Pintzas, A. (2007). Quercetin enhances TRAIL-mediated apoptosis in colon cancer cells by inducing the accumulation of death receptors in lipid rafts. Molecular cancer therapeutics 6:2591-2599.
  • Soyocak, A. Turgut Coşan, D. Başaran, A. Değirmenci, İ. and Güneş, H.V. (2009). The Association Between Apoptotic Bak Protein And Quercetin in Breast and Colon Cancer Cell Lines. FABAD J. Pharm. Sci 34:83-89.
  • Nakayama, Y. Sakamoto, H. Satoh, K. and Yamamoto, T. (2000). Tamoxifen and gonadal steroids inhibit colon cancer growth in association with inhibition of thymidylate synthase, survivin and telomerase expression through estrogen receptor beta mediated system. Cancer letters 161:63-71.
  • Shen, L.-Z. Hua, Y.-B. Yu, X.-M. Xu, Q. Chen, T. Wang, J.-H. and Wu, W.-X. (2005). Tamoxifen can reverse multidrug resistance of colorectal carcinoma in vivo. World J Gastroenterol 11:1060-1064.
  • Ziv, Y. Gupta, M. Milsom, J. Vladisavljevic, A. Brand, M. and Fazio, V. (1993). The effect of tamoxifen and fenretinimide on human colorectal cancer cell lines in vitro. Anticancer research 14:2005-2009.
  • Ziv, Y. Gupta, M. Milsom, J. Vladisavljevic, A. Kitago, K. and Fazio, V. (1995). The effect of tamoxifen on established human colorectal cancer cell lines in vitro. Anticancer research 16:3767-3771.
  • Motylewska, E. Ławnicka, H. and Mełeń- Mucha, G. (2007). Oestradiol and tamoxifen inhibit murine Colon 38 cancer growth and increase the cytotoxic effect of fluorouracil. Endokrynologia Polska 58:426-434.
  • Leo, A. Messa, C. Cavallini, A. and Linsalata, M. (2001). Estrogens and colorectal cancer. Current Drug Targets-Immune, Endocrine & Metabolic Disorders 1:1-12.
  • Cosan, D.T. Soyocak, A. Basaran, A. Degirmenci, İ. Gunes, H.V. and Sahin, F.M. (2011). Effects of various agents on DNA fragmentation activities in adenocarcinoma cell lines. Molecular biology reports 38:2463-2469. . enzyme
Year 2015, Volume: 37 Issue: 2, 14 - 20, 25.12.2015

Abstract

References

  • Johnson, D.Y. Wadhwa, S. and Johnson, F.E. (2013). Colon and Rectum Carcinoma. In Patient Surveillance After Cancer Treatment: Springer. 179-183.
  • Konstantinopoulos, P. Kominea, A. Vandoros, G. Sykiotis, G. Andricopoulos, P. Varakis, I. Sotiropoulou-Bonikou, G. and Papavassiliou, A. (2003). Oestrogen receptor beta (ERβ) is abundantly expressed in normal colonic mucosa, but declines in colon adenocarcinoma paralleling the tumour's dedifferentiation. European Journal of Cancer 39:1251-1258.
  • Campbell-Thompson, M. Lynch, I.J. and Bhardwaj, B. (2001). Expression of estrogen receptor (ER) subtypes and ERbeta isoforms in colon cancer. Cancer Res 61:632-640.
  • Picariello, L. Fiorelli, G. Martineti, V. Tognarini, I. Pampaloni, B. Tonelli, F. and Brandi, M.L. (2002). Growth response of colon cancer cell lines to selective estrogen receptor modulators. Anticancer research 23:2419-2424.
  • Rajamanickam, S. and Agarwal, R. (2008). Natural products and colon cancer: current status and future prospects. Drug Dev Res 69:460-471.
  • van Erk, M.J. Roepman, P. van der Lende, T.R. Stierum, R.H. Aarts, J. van Bladeren, P.J. and van Ommen, B. (2005). Integrated assessment by multiple gene expression analysis anticancer–related cancer cells in vitro. European journal of nutrition 44:143-156. bioactivity on mechanisms in colon
  • Galluzzo, P. Martini, C. Bulzomi, P. Leone, S. Bolli, A. Pallottini, V. and Marino, M. (2009). Quercetin‐induced apoptotic cascade in cancer cells: Antioxidant versus estrogen receptor α‐ dependent mechanisms. Molecular nutrition & food research 53:699-708.
  • Gibellini, L. Pinti, M. Nasi, M. Montagna, J.P. De Biasi, S. Roat, E. Bertoncelli, L. Cooper, E.L. and Cossarizza, A. (2011). Quercetin and cancer Complementary and Alternative Medicine 2011. Evidence-Based
  • Bulzomi, P. Galluzzo, P. Bolli, A. Leone, S. Acconcia, F. and Marino, M. (2012). The pro‐ apoptotic effect of quercetin in cancer cell lines requires ERβ‐dependent signals. Journal of Cellular Physiology 227:1891-1898.
  • Kumar, R. Verma, V. Jain, A. Jain, R.K. Maikhuri, J.P. and Gupta, G. (2011). Synergistic chemoprotective mechanisms of dietary phytoestrogens in a select combination against prostate cancer. J Nutr Biochem 22:723-731.
  • Khalkhali-Ellis, Z. Kirschmann, D.A. Edwards, E.M. Rezaie- Thompson, M. Vasef, M.A. Gruman, L.M. Seftor, R.E. Norwood, L.E. and Hendrix, M.J. (2004). Regulating the Tumor Suppressor Gene Maspin in Breast Cancer Cells A Potential Mechanism for the Anticancer Properties of Tamoxifen. Clinical cancer research 10:449-454. Christian, A.L.
  • Petinari, L. Kohn, L.K. de Carvalho, J.E. and Genari, S.C. (2004). Cytotoxicity of tamoxifen in normal and tumoral cell lines and its ability to induce cellular transformation in vitro. Cell biology international 28:531-539.
  • Aldous, W.K. Marean, A.J. DeHart, M.J. Matej, L.A. and Moore, K.H. (1999). Effects of tamoxifen on telomerase activity in breast carcinoma cell lines. Cancer 85:1523-1529. 14. Cosan, D. Soyocak, A. Basaran, A. Degirmenci, I. and Güneş, H.V. (2009). The effects of resveratrol and tannic acid on apoptosis in colon adenocarcinoma cell line. Saudi Med J 30:191-195.
  • Kim, W.K. Bang, M.H. Kim, E.S. Kang, N.E. Jung, K.C. Cho, H.J. and Park, J.H. (2005). Quercetin decreases the expression of ErbB2 and ErbB3 proteins in HT-29 human colon cancer cells. J Nutr Biochem 16:155-162.
  • Shan, B.-E. Wang, M.-X. and Li, R.-q. (2009). Quercetin inhibit human SW480 colon cancer growth in association with inhibition of cyclin D1 and survivin expression through Wnt/β- catenin investigation 27:604-612. pathway. Cancer
  • Murtaza, I. Marra, G. Schlapbach, R. Patrignani, A. Künzli, M. Wagner, U. Sabates, J. and Dutt, A. (2006). A preliminary investigation demonstrating the effect of quercetin on the expression of genes related to cell‐cycle arrest, apoptosis and xenobiotic metabolism adenocarcinoma cells using DNA microarray. Biotechnology and applied biochemistry 45:29-36. CO115 colon‐
  • Kim, H.J. Kim, S.K. Kim, B.S. Lee, S.H. Park, Y.S. Park, B.K. Kim, S.J. Kim, J. Choi, C. Kim, J.S. et al. (2010). Apoptotic effect of quercetin on HT-29 colon cancer cells via the AMPK signaling pathway. J Agric Food Chem 58:8643-8650.
  • van der Woude, H. Gliszczyńska-Świgło, A. Struijs, K. Smeets, A. Alink, G.M. and Rietjens, I.M. (2003). Biphasic modulation of cell concentrations physiologically relevant in humans. Cancer letters 200:41-47. at
  • Ak, A. Başaran, A. Dikmen, M. Coşan, D.T. Değirmenci, İ. and Güneş, H.V. (2011). Evaluation of Effects of Quercetin (3, 3’, 4’, 5, 7-pentohidroxyflavon) on Apoptosis and Telomerase Enzyme Activity in MCF-7 and NIH-3T3 Tamoxifen. Balkan Medical Journal 28:293- 299. Compared with
  • Choi, J.A. Kim, J.Y. Lee, J.Y. Kang, C.M. Kwon, H.J. Yoo, Y.D. Kim, T.W. Lee, Y.S. and Lee, S.J. (2001). Induction of cell cycle arrest and apoptosis in human breast cancer cells by quercetin. Int J Oncol 19:837-844.
  • Nichenametla, S.N. Taruscio, T.G. Barney, D.L. and Exon, J.H. (2006). A review of the effects and mechanisms of polyphenolics in cancer. Critical reviews in food science and nutrition 46:161-183.
  • Rodgers, E.H. and Grant, M.H. (1998). The effect of the flavonoids, quercetin, myricetin and epicatechin on the growth and enzyme activities of MCF7 human breast cancer cells. Chemico-biological interactions 116:213-228.
  • Psahoulia, F.H. Drosopoulos, K.G. Doubravska, L. Andera, L. and Pintzas, A. (2007). Quercetin enhances TRAIL-mediated apoptosis in colon cancer cells by inducing the accumulation of death receptors in lipid rafts. Molecular cancer therapeutics 6:2591-2599.
  • Soyocak, A. Turgut Coşan, D. Başaran, A. Değirmenci, İ. and Güneş, H.V. (2009). The Association Between Apoptotic Bak Protein And Quercetin in Breast and Colon Cancer Cell Lines. FABAD J. Pharm. Sci 34:83-89.
  • Nakayama, Y. Sakamoto, H. Satoh, K. and Yamamoto, T. (2000). Tamoxifen and gonadal steroids inhibit colon cancer growth in association with inhibition of thymidylate synthase, survivin and telomerase expression through estrogen receptor beta mediated system. Cancer letters 161:63-71.
  • Shen, L.-Z. Hua, Y.-B. Yu, X.-M. Xu, Q. Chen, T. Wang, J.-H. and Wu, W.-X. (2005). Tamoxifen can reverse multidrug resistance of colorectal carcinoma in vivo. World J Gastroenterol 11:1060-1064.
  • Ziv, Y. Gupta, M. Milsom, J. Vladisavljevic, A. Brand, M. and Fazio, V. (1993). The effect of tamoxifen and fenretinimide on human colorectal cancer cell lines in vitro. Anticancer research 14:2005-2009.
  • Ziv, Y. Gupta, M. Milsom, J. Vladisavljevic, A. Kitago, K. and Fazio, V. (1995). The effect of tamoxifen on established human colorectal cancer cell lines in vitro. Anticancer research 16:3767-3771.
  • Motylewska, E. Ławnicka, H. and Mełeń- Mucha, G. (2007). Oestradiol and tamoxifen inhibit murine Colon 38 cancer growth and increase the cytotoxic effect of fluorouracil. Endokrynologia Polska 58:426-434.
  • Leo, A. Messa, C. Cavallini, A. and Linsalata, M. (2001). Estrogens and colorectal cancer. Current Drug Targets-Immune, Endocrine & Metabolic Disorders 1:1-12.
  • Cosan, D.T. Soyocak, A. Basaran, A. Degirmenci, İ. Gunes, H.V. and Sahin, F.M. (2011). Effects of various agents on DNA fragmentation activities in adenocarcinoma cell lines. Molecular biology reports 38:2463-2469. . enzyme
There are 31 citations in total.

Details

Primary Language English
Journal Section ORİJİNAL MAKALE
Authors

Didem Coşan This is me

Ahu Soyocak This is me

Ayşe Başaran This is me

İrfan Değirmenci This is me

Hasan Güneş This is me

Cengiz Bal This is me

Publication Date December 25, 2015
Published in Issue Year 2015 Volume: 37 Issue: 2

Cite

Vancouver Coşan D, Soyocak A, Başaran A, Değirmenci İ, Güneş H, Bal C. HOW DOES QUERCETIN AND TAMOXIFEN AFFECT THE APOPTOSIS OF COLON CANCER CELLS?. Osmangazi Tıp Dergisi. 2015;37(2):14-20.


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