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Effects of Curcumin on Apoptosis in “In Vivo” Solid Ehrlich Ascites Tumor Model in Balb-C Mice

Year 2014, Volume: 40 Issue: 2, 183 - 190, 22.07.2014

Abstract

Curcumin is the yellow pigment in turmeric (Curcuma longa L) that is widely used as a spice, food coloring (curry) and preservative. Curcumin has a wide range of pharmacological properties including anti-inflammatory, anti-tumor promoter and anti-oxidant effects. In this study, the development and quantity of apoptosis in tumor tissue of solid Ehrlich Ascites Tumor model developed balb-c mouse by applying 100 mg/kg curcumin in different time periods were investigated. For this aim; 54 Balb-c female mice, constituted in vivo tumor by subcutaneous injection of 3x106 EAT cells, were divided into 3 experimental and 3 control groups. Using gavage method, 100 mg/kg curcumin dissolved in 9% alcohol was applied to experimental groups, 9% alcohol was applied to control groups in different time intervals. Long and short diameters measurement, and Terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin Nick End Labeling (TUNEL) and hematoxylin-eosin staining were applied to the extracted tumors of all groups and findings were supported with electron microscopic (TEM) evaluations. In long and short diameter measurement of acquired tumors, no significant differences were obtained (P>0.05). In microscopic evaluations different results were obtained from cell count of all groups. More apoptotic cells were determined in experimental group 2 (P<0.001) and 3 (P<0.05) than their control groups. According to statistical analysis, there was no significant difference between experimental group 1 that received longest-term curcumin and control 1 (P>0.05). Overall, the long-term 100 mg/kg applications of curcumin do not have any effect on apoptosis.

Key Words: Apoptosis, curcumin, ehrlich ascites tumor, mice

References

  • Babu, P.S., Srinivasan, K., 1997. Hypolipidemic action of curcumin the active principle of turmeric (curcuma longa) in streptozotocin induced diabetic rats. Molecular and Cellular Biochemistry 166, 169-175.
  • Babu, P.S., Srinivasan, K., 1998. Amelioration of renal lesions associated with diabetes by diatery curcumin in streptozotocin diabetes rats. Molecular and Cellular Biochemistry 181, 87
  • Chan, M.M-Y., Huang, H.I., Fenton, M.R., Fong, D., 1998. In vivo inhibition of nitric oxide synthase gene expression by curcumin, a cancer preventive natural product with antiinflammatory properties. Biochemical Pharmacology 55, 1955-1962.
  • Chen, Y.C., Kuo T.C., Lin-Shiau, S.Y., Lin, J.K., 19 Inducton of HSP70 gene expression by modulation of Ca +2 ion and cellular p53 protein by curcumin in colorectal carcinoma cells. Molecular Carcinogenesis 17 (Suppl. 4), 2242
  • Conney, A.H., Lysz, T., Ferraro, T, Abiddi, T.F., Manchand, P.S., Laskin, J.D., Huang, M.T., 19 Inhibitory effects of curcumin and some related dietary compounds on tumor promotion and arachidonic acid metabolism in mouse skin. Advances in Enzyme Regulation 31, 385-396. Cummings, M.C., Winterford, C.M., Walker, N.I., 19 Apoptosis: Histology for Pathologists. 2th ed. Chapter 1, 3-21. Philadelphia. Huang, M.T., Wang, Z.Y., Georgiadis, C.A., Laskin, J.D., Conney, A.H., 1992. Inhibitory effects of curcumin on tumor initiation by benzo   pyrene and 7,12-dimethylbenz  anthracene. Carsinogenezis, 13, 2183-2186.
  • Jang, M.H., Shin, M.C., Shin, H.S., Kim, K.H., Park, H.J., Kim, E.H., Kim, C.J., 2002. Alcohol induces apoptosis in TM3 mouse Leyding cells via Bax-dependent caspase-3 activation. European Journal of Pharmacology 449, 39-45.
  • Jaruga, E., Salvioli, S., Dobrucki, J., Chrul, S., Pikula, J.B., Sikora, E., Franceschi, C., Cossarizza, A., Bartosz, G., 1998a. Apoptosislike reversible changes in plasma membrane asymmetry and permeability and transient modifications in mitochondrial membrane potential induced by curcumin in rat thymocytes. Federation of European Biochemical Societies Letters 433, 287-293.
  • Jaruga, E., Zmijewska, A.B., Sikora, E., Skierski, J., Radziszewska, E., Piwocka, K., Bartosz, G., 1998b. Glutathione-independent mecanism of apoptosis inhibition by curcumin in rat thymocytes. Biochemical Pharmacology 56, 961-9
  • Jiang, M.C., Yang-Yen, H.F., Yen, J.J., Lin, J.K., 19 Curcumin induces apoptosis in immortaned NIH 3T3 and malignant cancer cell lines. Nutrition and Cancer 26 (Suppl.1), 111 Khar, A., Ali, A.M., Pardhasaredhi, B.V., Begum, Z., Anjum, R., 1999. Antitumor activity of curcumin is mediated through the induction of apoptosis in AK-5 tumor cells. Federation of European Biochemical Societies Letters 19, 445 (1), 165-168.
  • Kuo, M.L., Huang, T.S., Lin, J.K., 1996. Curcumin an antioxidant and anti-tumor promoter, induces apoptosis in human leucemia cells. Biochimica et Biophysica Acta 1317 (Suppl.), 95-100.
  • Limtrakul, P., Lipigorngoson, S., Namwong, O., Apisariyakul, A., Dunn, F.W., 19 Inhibitory effect of diatery curcumin on skin carsinogenesis in mice. Cancer Letters 116, 197-20 Linke, S.P., Clarkin, K.C., Wahl, G.M., 1997. p53 mediates permanent arrest over multiple cell cycles in response to gamma irradition. Cancer Research 57, 1171-1179.
  • Piwocka, K., Jaruga, E., Skierski, J., Gradzka, I., Sikora, E., 2001. Effect of glutathione depletion on caspase-3 independent apoptosis pathway induced by curcumin in jurkat cells. Free Radical Biology and Medicine 31, 6706
  • Ramachandran, C., You, W., 1999. Differential sensitivity of human mammary epithelial and breast carcinoma cell lines to curcumin. Breast Cancer Research and Treatment 54 (Suppl.3), 269-2
  • Ruby, A.J., Kuttan, G., Babu, D.K., Rajasekharan, K.N., Kuttan, R., 1995. Anti-tumor and antioxidant activity of natural curcuminoids. Cancer Letters 94, 79-83.
  • Scartezzini, P., Speroni, E., 2000. Review on some plants of Indian traditional medicine with antioxidant activity. Journal of Ethnopharmacology 71, 23-43.
  • Sikora, E., Grassilli, E., Bellessia, E., Troiano, L., Franceschi, C., 19 Studies of the relationship between cell proliferation and cell death: AP-1 DNA- binding activity during concavalin A-induced proliferation or dexamethasone- induced apoptosis of rat thymocytes. Biochemical and Biophysical Research Communications 192, 386-391.

EHRLICH ASCITES TÜMÖRÜ İLE BALB-C FARELERDE OLUŞTURULMUŞ SOLİD TÜMÖR MODELİNDE CURCUMİNİN APOPTOZ ÜZERİNE ETKİLERİ

Year 2014, Volume: 40 Issue: 2, 183 - 190, 22.07.2014

Abstract

Curcumin, turmeric (Curcuma longa L) de bulunan, yaygın olarak baharat, yiyecek reklendirici ve koruyucu olarak kullanılan sarı renkli pigmentdir. Curcumin anti-inflamatuar, anti-tümöral ve anti-oksidan gibi çeşitli farmakolojik özelliklerinden dolayı yaygın bir kullanıma sahiptir. Bu çalışmada, Balb-c farelerde geliştirilen Ehrlich Ascites Tümör modelinde farklı periyotlarda 100 mg/kg curcumin uygulamasının apoptosis miktarı ve gelişimi üzerine etkisi incelendi. Bu amaçla; 54 adet Balb-c dişi fare, in vivo tumor oluşturmak için 3x106 EAT hücresinin subkutan olarak enjeksiyonunu takiben 3 deney ve 3 kontrol grubuna ayrıldı. Gavaj metodu kullanılarak %9 alkol içerisinde çözündürülen 100 mg/kg curcumin deney gruplarına, %9 alkol kontrol gruplarına farklı zaman aralıklarında uygulandı. Tüm gruplardan alınan tümörlerde kısa ve uzun çap ölçümleri, Terminal deoksiribonükleotidil trasferaz-aracılı dUTP-digoksigenin uç işaretleme tekniği (TUNEL) ve hematoksilen-eosin boyama uygulandı. Bulgular ayrıca elektron mikroskobik (TEM) değerlendirmelerle desteklendi. Tümörlerden elde edilen kısa ve uzun çap uzunluklarında herhangi bir farklılık görülmedi (P>0,05). Tüm gruplardan elde edilen hücre sayımlarında mikroskobik değerlendirmelerde farklı sonuçlar gözlendi. Deney Grubu 2 (P<0,001) ve 3 (P<0,05)’de ve Kontrol Gruplarına gore daha fazla apoptotik hücre tespit edildi. İstatistiksel verilere göre, uzun sure curcumin uygulaması yapılan Deney Grubu 1 ve bu gruba ait Kontrol 1 grubu arasında anlamlı bir fark yoktu (P>0,05). Genel olarak, Curcumin’in uzun sure 100 mg/kg uygulamasının apoptoz üzerinde herhangi bir etkisi yoktur.

Anahtar Kelimeler: Apoptoz, curcumin, ehrlich ascites tümör, fare

References

  • Babu, P.S., Srinivasan, K., 1997. Hypolipidemic action of curcumin the active principle of turmeric (curcuma longa) in streptozotocin induced diabetic rats. Molecular and Cellular Biochemistry 166, 169-175.
  • Babu, P.S., Srinivasan, K., 1998. Amelioration of renal lesions associated with diabetes by diatery curcumin in streptozotocin diabetes rats. Molecular and Cellular Biochemistry 181, 87
  • Chan, M.M-Y., Huang, H.I., Fenton, M.R., Fong, D., 1998. In vivo inhibition of nitric oxide synthase gene expression by curcumin, a cancer preventive natural product with antiinflammatory properties. Biochemical Pharmacology 55, 1955-1962.
  • Chen, Y.C., Kuo T.C., Lin-Shiau, S.Y., Lin, J.K., 19 Inducton of HSP70 gene expression by modulation of Ca +2 ion and cellular p53 protein by curcumin in colorectal carcinoma cells. Molecular Carcinogenesis 17 (Suppl. 4), 2242
  • Conney, A.H., Lysz, T., Ferraro, T, Abiddi, T.F., Manchand, P.S., Laskin, J.D., Huang, M.T., 19 Inhibitory effects of curcumin and some related dietary compounds on tumor promotion and arachidonic acid metabolism in mouse skin. Advances in Enzyme Regulation 31, 385-396. Cummings, M.C., Winterford, C.M., Walker, N.I., 19 Apoptosis: Histology for Pathologists. 2th ed. Chapter 1, 3-21. Philadelphia. Huang, M.T., Wang, Z.Y., Georgiadis, C.A., Laskin, J.D., Conney, A.H., 1992. Inhibitory effects of curcumin on tumor initiation by benzo   pyrene and 7,12-dimethylbenz  anthracene. Carsinogenezis, 13, 2183-2186.
  • Jang, M.H., Shin, M.C., Shin, H.S., Kim, K.H., Park, H.J., Kim, E.H., Kim, C.J., 2002. Alcohol induces apoptosis in TM3 mouse Leyding cells via Bax-dependent caspase-3 activation. European Journal of Pharmacology 449, 39-45.
  • Jaruga, E., Salvioli, S., Dobrucki, J., Chrul, S., Pikula, J.B., Sikora, E., Franceschi, C., Cossarizza, A., Bartosz, G., 1998a. Apoptosislike reversible changes in plasma membrane asymmetry and permeability and transient modifications in mitochondrial membrane potential induced by curcumin in rat thymocytes. Federation of European Biochemical Societies Letters 433, 287-293.
  • Jaruga, E., Zmijewska, A.B., Sikora, E., Skierski, J., Radziszewska, E., Piwocka, K., Bartosz, G., 1998b. Glutathione-independent mecanism of apoptosis inhibition by curcumin in rat thymocytes. Biochemical Pharmacology 56, 961-9
  • Jiang, M.C., Yang-Yen, H.F., Yen, J.J., Lin, J.K., 19 Curcumin induces apoptosis in immortaned NIH 3T3 and malignant cancer cell lines. Nutrition and Cancer 26 (Suppl.1), 111 Khar, A., Ali, A.M., Pardhasaredhi, B.V., Begum, Z., Anjum, R., 1999. Antitumor activity of curcumin is mediated through the induction of apoptosis in AK-5 tumor cells. Federation of European Biochemical Societies Letters 19, 445 (1), 165-168.
  • Kuo, M.L., Huang, T.S., Lin, J.K., 1996. Curcumin an antioxidant and anti-tumor promoter, induces apoptosis in human leucemia cells. Biochimica et Biophysica Acta 1317 (Suppl.), 95-100.
  • Limtrakul, P., Lipigorngoson, S., Namwong, O., Apisariyakul, A., Dunn, F.W., 19 Inhibitory effect of diatery curcumin on skin carsinogenesis in mice. Cancer Letters 116, 197-20 Linke, S.P., Clarkin, K.C., Wahl, G.M., 1997. p53 mediates permanent arrest over multiple cell cycles in response to gamma irradition. Cancer Research 57, 1171-1179.
  • Piwocka, K., Jaruga, E., Skierski, J., Gradzka, I., Sikora, E., 2001. Effect of glutathione depletion on caspase-3 independent apoptosis pathway induced by curcumin in jurkat cells. Free Radical Biology and Medicine 31, 6706
  • Ramachandran, C., You, W., 1999. Differential sensitivity of human mammary epithelial and breast carcinoma cell lines to curcumin. Breast Cancer Research and Treatment 54 (Suppl.3), 269-2
  • Ruby, A.J., Kuttan, G., Babu, D.K., Rajasekharan, K.N., Kuttan, R., 1995. Anti-tumor and antioxidant activity of natural curcuminoids. Cancer Letters 94, 79-83.
  • Scartezzini, P., Speroni, E., 2000. Review on some plants of Indian traditional medicine with antioxidant activity. Journal of Ethnopharmacology 71, 23-43.
  • Sikora, E., Grassilli, E., Bellessia, E., Troiano, L., Franceschi, C., 19 Studies of the relationship between cell proliferation and cell death: AP-1 DNA- binding activity during concavalin A-induced proliferation or dexamethasone- induced apoptosis of rat thymocytes. Biochemical and Biophysical Research Communications 192, 386-391.
There are 16 citations in total.

Details

Primary Language English
Journal Section Research Article
Authors

Elif Ikıtımur-armutak

Mehmet Gurtekın This is me

Publication Date July 22, 2014
Published in Issue Year 2014 Volume: 40 Issue: 2

Cite

APA Ikıtımur-armutak, E., & Gurtekın, M. (2014). Effects of Curcumin on Apoptosis in “In Vivo” Solid Ehrlich Ascites Tumor Model in Balb-C Mice. İstanbul Üniversitesi Veteriner Fakültesi Dergisi, 40(2), 183-190. https://doi.org/10.16988/iuvfd.03591
AMA Ikıtımur-armutak E, Gurtekın M. Effects of Curcumin on Apoptosis in “In Vivo” Solid Ehrlich Ascites Tumor Model in Balb-C Mice. iuvfd. July 2014;40(2):183-190. doi:10.16988/iuvfd.03591
Chicago Ikıtımur-armutak, Elif, and Mehmet Gurtekın. “Effects of Curcumin on Apoptosis in ‘In Vivo’ Solid Ehrlich Ascites Tumor Model in Balb-C Mice”. İstanbul Üniversitesi Veteriner Fakültesi Dergisi 40, no. 2 (July 2014): 183-90. https://doi.org/10.16988/iuvfd.03591.
EndNote Ikıtımur-armutak E, Gurtekın M (July 1, 2014) Effects of Curcumin on Apoptosis in “In Vivo” Solid Ehrlich Ascites Tumor Model in Balb-C Mice. İstanbul Üniversitesi Veteriner Fakültesi Dergisi 40 2 183–190.
IEEE E. Ikıtımur-armutak and M. Gurtekın, “Effects of Curcumin on Apoptosis in ‘In Vivo’ Solid Ehrlich Ascites Tumor Model in Balb-C Mice”, iuvfd, vol. 40, no. 2, pp. 183–190, 2014, doi: 10.16988/iuvfd.03591.
ISNAD Ikıtımur-armutak, Elif - Gurtekın, Mehmet. “Effects of Curcumin on Apoptosis in ‘In Vivo’ Solid Ehrlich Ascites Tumor Model in Balb-C Mice”. İstanbul Üniversitesi Veteriner Fakültesi Dergisi 40/2 (July 2014), 183-190. https://doi.org/10.16988/iuvfd.03591.
JAMA Ikıtımur-armutak E, Gurtekın M. Effects of Curcumin on Apoptosis in “In Vivo” Solid Ehrlich Ascites Tumor Model in Balb-C Mice. iuvfd. 2014;40:183–190.
MLA Ikıtımur-armutak, Elif and Mehmet Gurtekın. “Effects of Curcumin on Apoptosis in ‘In Vivo’ Solid Ehrlich Ascites Tumor Model in Balb-C Mice”. İstanbul Üniversitesi Veteriner Fakültesi Dergisi, vol. 40, no. 2, 2014, pp. 183-90, doi:10.16988/iuvfd.03591.
Vancouver Ikıtımur-armutak E, Gurtekın M. Effects of Curcumin on Apoptosis in “In Vivo” Solid Ehrlich Ascites Tumor Model in Balb-C Mice. iuvfd. 2014;40(2):183-90.