Curcumin promotes extrinsic apoptosis in canine osteosarcoma cells

Authors

DOI:

https://doi.org/10.33448/rsd-v9i10.9231

Keywords:

Cytotoxicity; D-17; Immunocytochemistry; Cell death.

Abstract

Canine osteosarcoma is the most common bone tumor in dogs. It has an intense metastatic capacity, and the patient survival rate is low in this disease. Curcumin, the most important compound derived from the plant Curcuma longa L., has been widely studied and has shown considerable antineoplastic effects against many tumors. This study aims to identify the activation of specific proteins of apoptosis pathways, tumor survival, and poor prognosis of this disease in D-17 osteosarcoma cells. For this, the cells were cultured and treated with curcumin at concentrations of 20μM, 50 μM, and 100 μM in prepared and fixed slides. Subsequently, we performed the immunocytochemical analysis with anti-caspase3, anti-JNK, anti-AMPK, anti-p53, anti-AKT, and anti-mTOR antibodies. Curcumin activated the cell-death proteins caspase-3, JNK, and AMPK, reduced the expression of the mutated p53 protein, and did not alter the AKT and mTOR proteins in canine osteosarcoma cells in vitro. Thus, curcumin induces extrinsic apoptosis mediated by caspase, JNK, and cAMP/AMPK in canine osteosarcoma cells. Besides, it has the potential to improve the tumor prognosis of this disease by inactivating the mutated p53. However, it does not interfere with AKT/mTOR expression, related to tumor proliferation and survival. Such results will serve as a basis for future studies that analyze the effect of curcumin in vivo on this disease.

References

Amarante-Mendes G. P., & Green DR. (1999). The regulation of apoptotic cell death. Braz J Med Biol Res. 32:1053-61.

Anand P., Sundaram C., Jhurani S., Kunnumakkara A. B., & Aggarwal BB. (2008). Curcumin and cancer: an "old-age" disease with an "age-old" solution. Cancer Lett. 267:133-164.

Arnhold E. (2013). Package in the R environment for analysis of variance and complementary analyses. Brazilian Journal of Veterinary Research and Animal Science. 50(6):488-492.

Ashour A. A., Abdel-Aziz A. A., Mansour A. M., Alpay S. N., Huo L., & Ozpolat B. (2014). Targeting elongation factor-2 kinase (eEF-2K) induces apoptosis in human pancreatic câncer cells. Apoptosis. 19:241-258.

Balasubramanian S., & Eckert R. L. (2007). Curcumin suppresses AP1 transcription factor-dependent differentiation and activates apoptosis in human epidermal keratinocytes. J. Biol. Chem. 282:6707-6715.

Behrens A., Jochum W., Sibilia M., & Wagner E. F. (2000). Oncogenic transformation by ras and fos is mediated by c-Jun N-terminal phosphorylation. Oncogene. 19(22):2657.

Cavalcanti J. N., Amstalden E. M. I., Guerra J. L., & Magna L. C. (2004). Osteossarcoma em cães: estudo clínico-morfológico e correlação prognóstica. Brazilian Journal of Veterinary Research and Animal Science. 41(5):299- 305.

Chin K. V., Yang W. L., Ravatn R., Kita T., Reitman E., Vettori D., Cvijic M. E., Shin M., & Iacono L. (2002). Reinventing the wheel of cyclic AMP: novel mechanisms of cAMP signaling. Ann N Y Acad Sci. 968:49-64.

Collett G. P., & Campbell F. C. (2004). Curcumin induces c-jun N-terminal kinase-dependent apoptosis in HCT116 human colon cancer cells. Carcinogenesis. 25(11):183-2189.

De Smaele, E., Zazzeroni, F., Papa, S., Nguyen, D. U., Jin, R., Jones, J., & Franzoso, G. (2001). Induction of gadd45 β by NF-κ B downregulates pro-apoptotic JNK signalling. Nature. 414(6861):308-313.

Fan, T. J., Han, L. H., Cong, R. S., & Liang, J. (2005). Caspase family proteases and apoptosis. Acta biochimica et biophysica Sinica. 37(11):719-727.

Fedchenko N., & Reifenrath J. (2014). Different approaches for interpretation and reporting of immunohistochemistry analysis results in the bone tissue–a review. Diagnostic pathology. 9(1):221.

Fitzgibbons P. L., Dillon D. A., Alsabeh R., Berman M. A., Hayes D. F., Hicks D. G., Hughes K. S., & Nofech-Mozes S. (2014). Template for reporting results of biomarker testing of specimens from patients with carcinoma of the breast. Arch Pathol Lab Med. 138:595-601.

Fridman J. S., & Lowe S. W. (2003). Control of apoptosis by p53. Oncogene. 22:9030-9040.

Galluzzi, L., Kepp, O., & Kroemer, G. (2016). Mitochondrial regulation of cell death: a phylogenetically conserved control. Microbial Cell. 3(3):101.

George P. (2011). p53 how crucial is its role in cancer. Int J Curr Pharm Res. 3:19-25.

Gopal P. K., Paul M., & Paul S. (2014). Curcumin induces caspase mediated apoptosis in JURKAT cells by disrupting the redox balance. Asian Pac J Cancer Prev. 15(1):93-100.

Greenblatt M. S., Bennett W. P., & Hollstein M. (1994). Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res. 54:4855-4878.

Guo H., Xu Y. M., Ye Z. Q., Yu J. H., & Hu X. Y. (2013). Curcumin induces cell cycle arrest and apoptosis of prostate cancer cells by regulating the expression of IκBα, c-Jun and androgen receptor. Die Pharmazie-An International Journal of Pharmaceutical Sciences, 68(6), 431-434.

Hasima, N., & Aggarwal, B. B. (2012). Cancer-linked targets modulated by curcumin. International journal of biochemistry and molecular biology. 3(4):328.

Hu S., Xu Y., Meng L., Huang L., & Sun H. (2018). Curcumin inhibits proliferation and promotes apoptosis of breast cancer cells. Experimental and therapeutic medicine. 16(2):1266-1272.

Itahana K., Dimri G., & Campisi J. (2001). Regulation of cellular senescence by p53. Eur J Biochem. 268:2784-2791.

Jin Y., Tipoe G. L., Liong E. C., Lau T. Y. H., Fung P. C. W., & Leung K. M. (2001). Overexpression of BMP-2/4, −5 and BMPR-IA associated with malignancy of oral epithelium. Oral Oncol. 37:225-233.

Johnson A. S., Couto C. G., & Weghorst C. M. (1998). Mutation of the p53 tumor suppressor gene in spontaneously occurring osteosarcomas of the dog. Carcinogênese. 19:213-217.

Jordan B. C., Mock C. D., Thilagavathi R., & Selvam C. (2016). Molecular mechanisms of curcumin and its semisynthetic analogues in prostate cancer prevention and treatment. Life Sci. 152:135-144.

Khan, A. Q., Siveen, K. S., Prabhu, K. S., Kuttikrishnan, S., Akhtar, S., Shaar, A., & Uddin, S. (2018). Curcumin-mediated degradation of S-phase kinase protein 2 induces cytotoxic effects in human papillomavirus-positive and negative squamous carcinoma cells. Frontiers in Oncology. 8:399.

Kim E. K., & Choi E. J. (2010). Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta. 1802:396-405.

Kirpensteijn J., Kik M., Teske E., & Rutteman G. R. (2008). TP53 gene mutations in canine osteosarcoma. Veterinary Surgery. 37(5), 454-460.

Li J., Xiang S., Zhang Q., Wu J., Tang Q., Zhou J., Yang L., Chen Z., & Hann S. S. (2015). Combination of curcumin and bicalutamide enhanced the growth inhibition of androgen-independent prostate cancer cells through SAPK/JNK and MEK/ERK1/2-mediated targeting NF-kappaB/p65 and MUC1-C. J Exp Clin Cancer Res. 34:46.

Lim W., Jeong M., Bazer F. W., & Song G. (2016). Curcumin suppresses proliferation and migration and induces apoptosis on human placental choriocarcinoma cells via ERK1/2 and SAPK/JNK MAPK signaling pathways. Biology of reproduction. 95(4), 83-1.

Mirabello, L. J., Yeager, M., Mai, P. L., Gastier-Foster, J., Gorlick, R., Khanna, C., & Wunder, J. S. (2015). High prevalence of germline TP53 mutations in young osteosarcoma cases. 75:5574.

Moragoda L., Jaszewski R., & Majumdar A. P. (2001). Curcumin induced modulation of cell cycle and apoptosis in gastric and colon cancer cells. Anticancer Res. 21:873-878.

National Center for Biotechnology Information. (2020). PubChem Database. Compound Summary: Curcumin. https://pubchem.ncbi.nlm.nih.gov/compound/Curcumin. Accessed June 04.

Pan, W., Yang, H., Cao, C., Song, X., Wallin, B., Kivlin, R., & Wan, Y. (2008). AMPK mediates curcumin-induced cell death in CaOV3 ovarian cancer cells. Oncology reports. 20(6):1553-1559.

Pereira, A. S., Shitsuka, D. M., Parreira, F. J., & Shitsuka, R. (2018). Metodologia da pesquisa científica.[e-book]. Santa Maria. Ed. UAB/NTE/UFSM. Disponível em: https://repositorio. ufsm. br/bitstream/handle/1/15824/Lic_Computacao_Metodologia-Pesquisa-Cientifica. pdf.

Prokocimer M., & Rotter V. (1994). Structure and function of p53 in normal cells and their aberrations in cancer cells: projection on the hematologic cell lineages. Blood. 84:2391-3411.

Qian Y., & Chen X. (2013). Senescence regulation by the p53 protein family. Methods Mol Biol. 965:37-61.

Ray R. M., Jin S., Bavaria M. N., & Johnson L. R. (2011). Regulation of JNK activity in the apoptotic response of intestinal epithelial cells. American Journal of Physiology. 300(5):761-770.

Sappayatosok K., Maneerat Y., Swasdison S., Viriyavejakul P., Dhanuthai K., Zwang J., & Chaisri U. (2009). Expression of pro-inflammatory protein, iNOS, VEGF and COX-2 in oral squamous cell carcinoma (OSCC), relationship with angiogenesis and their clinico-pathological correlation. Med Oral Patol Oral Cir Bucal. 14:E319-E324.

Shackelford R. E., Kaufmann W. K., & Paules R. S. (1999). Cell cycle, checkpoint mechanism, and genotoxic stress. Environ Health Perspect. 107:5-24.

Szewczyk M., Lechowski R., & Zabielska K. (2015). What do we know about canine osteosarcoma treatment? Review. Veterinary Research Communications. 39(1):61-67.

Tait, S. W., & Green, D. R. (2010). Mitochondria and cell death: outer membrane permeabilization and beyond. Nature reviews Molecular cell biology. 11(9):621-632.

Tang G., Minemoto Y., Dibling B., Purcell N. H., Li Z., Karin M., & Lin A. (2001). Inhibition of JNK activation through NF-κ B target genes. Nature. 414(6861), 313-317.

Team RC. (2013). R: A language and environment for statistical computing.

Teiten M. H., Gaascht F., Cronauer M., Henry E., Dicato M., & Diederich M. (2011). Anti-proliferative potential of curcumin in androgen-dependent prostate cancer cells occurs through modulation of the Wingless signaling pathway. Int J Oncol. 38(3):603-611.

Tomeh M. A., Hadianamrei R., & Zhao X. (2019). A review of curcumin and its derivatives as anticancer agents. International journal of molecular sciences. 20(5):1033-1058.

Torlakovic E. E., Riddell R., Banerjee D., El-Zimaity H., Pilavdzic D., Dawe P., Magliocco A., Barnes P., Berendt R., Cook D., Gilks B., Williams G., Perez-Ordonez B., Wehrli B., Swanson P. E., Otis C. N., Nielsen S., Vyberg M., & Butany J. (2010). Canadian Association of Pathologists-Association canadienne des pathologistes National Standards Committee/Immunohistochemistry: best practice recommendations for standardization of immunohistochemistry tests. Am J Clin Pathol. 133:354-365.

Tsuchiya T., Sekine K. I., Hinohara S. I., Namiki T., Nobori T., & Kaneko Y. (2000). Analysis of the p16INK4, p14ARF, p15, TP53, and MDM2 genes and their prognostic implications in osteosarcoma and Ewing sarcoma. Cancer Genetics and Cytogenetics. 120(2):91–98.

Vallianou N. G., Evangelopoulos A., Schizas N., & Kazazis C. (2015). Potential anticancer properties and mechanisms of action of curcumin. Anticancer Res. 35:645-651.

Van Leeuwen, I. S., Cornelisse, C. J., Misdorp, W., Goedegebuure, S. A., Kirpensteijn, J., & Rutteman, G. R. (1997). P53 gene mutations in osteosarcomas in the dog. Cancer letters. 111(1-2):173-178.

Yang C. W., Chang C. L., Lee H. C., Chi C. W., Pan J. P., & Yang W. C. (2012). Curcumin induces the apoptosis of human monocytic leukemia THP-1 cells via the activation of JNK/ERK pathways. BMC complementary and alternative medicine. 12(1):1-8.

Yu T., Ji J., & Guo Y. L. (2013). MST1 activation by curcumin mediates JNK activation, Foxo3a nuclear translocation and apoptosis in melanoma cells. Biochemical and biophysical research communications. 441(1):53-58.

Yu, S., Shen, G., Khor, TO, Kim, JH, & Kong, AN (2008). A curcumina inibe Akt / alvo mamífero da sinalização da rapamicina através do mecanismo dependente da proteína fosfatase. Molecular cancer therapeutics. 7(9):2609-2620.

Zhang, C., Hao, Y., Wu, L., Dong, X., Jiang, N., Cong, B., & Zhao, X. (2018). Curcumin induces apoptosis and inhibits angiogenesis in murine malignant mesothelioma. International journal of oncology. 53(6):2531-2541.

Zhu G. H., Dai H. P., Shen Q., Ji O., Zhang Q., & Zhai Y. L. (2016). Curcumin induces apoptosis and suppresses invasion through MAPK and MMP signaling in human monocytic leukemia SHI-1 cells. Pharmaceutical biology. 54(8):1303-1311.

Zhu, G. H., Zhang, Q., Dai, H. P., Jl, O., & Shen, Q. (2013). Molecular mechanism of SHI-1 cell apoptosis induced by Puerariae Radix flavones in vitro. Zhongguo shi yan xue ye xue za zhi. 21(6):1423-1428.

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Published

16/10/2020

How to Cite

SOARES, N. P. .; NEPOMUCENO, L. L. .; CRUZ, V. de S. .; ARNHOLD, E. .; VIEIRA, V. de S. .; BORGES, J. C. de A. .; PEREIRA, D. K. S.; PEREIRA, K. F.; ARAÚJO, E. G. de . Curcumin promotes extrinsic apoptosis in canine osteosarcoma cells. Research, Society and Development, [S. l.], v. 9, n. 10, p. e7289109231, 2020. DOI: 10.33448/rsd-v9i10.9231. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/9231. Acesso em: 26 dec. 2024.

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Agrarian and Biological Sciences