Evaluation of the Effect of 1,3-Bis(4-Phenyl)-1H-1,2,3-Triazolyl-2-Propanolol on Gene Expression Levels of JAK2–STAT3, NF-κB, and SOCS3 in Cells Cultured from Biopsies of Mammary Lesions

详细信息    查看全文

• 作者：J. L. Malvaez Becerril ; J. G. Santillán Benítez…
• 关键词：Breast cancer ; JAK2 ; NF ; κB ; SOCS3 ; STAT3
• 刊名：Biochemical Genetics
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：53
• 期：11-12
• 页码：291-300
• 全文大小：362 KB
• 参考文献：Aizpurua JM, Azcune I, Fratila RM, Balentova E, Sagartzazu-Aizpurua M, Miranda JI (2010) Click synthesis of nonsymmetrical bis (1,2,3-triazoles). Organic Lett. 12(7):1584-587
  Babon JJ, Kershaw NJ, Murphy JM, Varghese LN, Laktyushin A, Young SN et al (2012) Suppression of cytokine signaling by SOCS3: characterization of the mode of inhibition and the basis of its specificity. Immunity 36(2):239-50PubMedCentral CrossRef PubMed
  Chávarri-Guerra Y, Villarreal-Garza C, Liedke PER, Knaul F, Mohar A, Finkelstein DM et al (2012) Breast cancer in Mexico: a growing challenge to health and the health system. Lancet Oncol 13(8):e335–e343CrossRef PubMed
  Duan Y-C, Ma Y-C, Zhang E, Shi X-J, Wang M-M, Ye X-W et al (2013) Design and synthesis of novel 1,2,3-triazole-dithiocarbamate hybrids as potential anticancer agents. Eur J Med Chem 62:11-9CrossRef PubMed
  Furth PA (2014) STAT signaling in different breast cancer sub-types. Mol Cell Endocrinol 382(1):612-15CrossRef PubMed
  German CL, Sauer BM, Howe CL (2011) The STAT3 beacon: IL-6 recurrently activates STAT 3 from endosomal structures. Exp Cell Res 317(14):1955-969PubMedCentral CrossRef PubMed
  González J, Pérez VM, Jiménez DO, López GL, Corona D, Cuevas EY (2011) Effect of temperature on triazole and bistriazole formation through copper-catalyzed alkyne–azide cycloaddition. Tetrahedron Lett 52:3514-517CrossRef
  Guo S, Liu M, Wang G, Torroella-Kouri M, Gonzalez-Perez RR (2012) Oncogenic role and therapeutic target of leptin signaling in breast cancer and cancer stem cells. Biochim et Biophys Acta (BBA). 1825(2):207-22PubMedCentral
  Gupta N, Grebhardt S, Mayer D (2012) Janus kinase 2—a novel negative regulator of estrogen receptor α function. Cell Signal 24(1):151-61CrossRef PubMed
  Harbeck N, Salem M, Nitz U, Gluz O, Liedtke C (2010) Personalized treatment of early-stage breast cancer: present concepts and future directions. Cancer Treat Rev 36(8):584-94CrossRef PubMed
  Haricharan S, Li Y (2014) STAT signaling in mammary gland differentiation, cell survival and tumorigenesis. Mol Cell Endocrinol 382(1):560-69CrossRef PubMed
  Hou Y-P, Sun J, Pang Z-H, Lv P-C, Li D-D, Yan L et al (2011) Synthesis and antitumor activity of 1,2,4-triazoles having 1,4-benzodioxan fragment as a novel class of potent methionine aminopeptidase type II inhibitors. Bioorg Med Chem 19(20):5948-954CrossRef PubMed
  Jardé T, Perrier S, Vasson M-P, Caldefie-Chézet F (2011) Molecular mechanisms of leptin and adiponectin in breast cancer. Eur J Cancer 47(1):33-3CrossRef PubMed
  Khandekar MJ, Cohen P, Spiegelman BM (2011) Molecular mechanisms of cancer development in obesity. Cancer 11:885-95
  Kumar K, Sagar S, Esau L, Kaur M, Kumar V (2012) Synthesis of novel 1H-1,2,3-triazole tethered C-5 substituted uracil–isatin conjugates and their cytotoxic evaluation. Eur J Med Chem 58:153-59CrossRef PubMed
  Li F, Sethi G (2010) Targeting transcription factor NF-κB to overcome chemoresistance and radioresistance in cancer therapy. Biochim et Biophys Acta (BBA) 1805(2):167-80
  Li F, Park Y, Hah J-M, Ryu J-S (2013) Synthesis and biological evaluation of 1-(6-methylpyridin-2-yl)-5-(quinoxalin-6-yl)-1,2,3-triazoles as transforming growth factor-β type 1 receptor kinase inhibitors. Bioorg Med Chem Lett 23(4):1083-086CrossRef PubMed
  Ling J, Kumar R (2012) Crosstalk between NFkB and glucocorticoid signaling: a potential target of breast cancer therapy. Cancer Lett 322(2):119-26CrossRef PubMed
  Linossi EM, Babon JJ, Hilton DJ, Nicholson SE (2013) Suppression of cytokine signaling: the SOCS perspective. Cytokine Growth Factor Rev 24(3):241-48CrossRef PubMed
  Moretti M, Bennett J, Tornatore L, Thotakura AK, Franzoso G (2012) Cancer: NF-κB regulates energy metabolism. Int J Biochem Cell Biol 44(12):2238-243CrossRef PubMed
  Murray AJ, Davies DM (2013) The genetics of breast cancer. Surgery (Oxford) 31(1):1-CrossRef
  Napoleone E, Cutrone A, Cugino D, Latella MC, Zurlo F, Iacoviello L et al (2012) Leptin upregulates tissue factor expression in human breast cancer MCF-7 cells. Thromb Res 129(5):641-47CrossRef PubMed
  Oeckinghaus A, Hayden MS, Ghosh S (2011) Crosstalk in NF-κB signaling pathways. Nature Inmunol 12(8):14
  Perks CM, Holly JMP (2011) Hormonal mechanisms underlying the relationship between obesity and breast cancer. Endocrinol Metab Clin North Am 40(3):485-07CrossRef PubMed
  Ray A, Cleary MP (2012) Obesity and breast cancer: a clinical biochemistry perspective. Clin Biochem 45(3):189-97CrossRef PubMed
  Santillán Benítez JG, Mendieta ZH, Gómez OLM, Torres JJJ, González BJM (2012) The tetrad BMI, leptin, leptin/adiponectin (L/A) ratio and CA 15-3 are reliable biomarkers of breast cancer. J Clin Lab Anal 00:1-
  Schweinfurth D, Strobel S, Sarkar B (2011) Expanding the scope of ‘Click-derived 1,2,3-triazole ligands: new palladium and platinum complexes. Inorg Chim Acta 374(1):253-60CrossRef
  Shanmugam MK, Radhamani K, G
• 作者单位：J. L. Malvaez Becerril (2)
  J. G. Santillán Benítez (1) (2)
  J. J. Torres Juárez (3)
  J. M. González Ba?ales (4)
  H. Mendieta Zerón (1)
  M. D. Hernández Navarro (2)
  
  2. Faculty of Chemistry, UAEMex, C.P. 50130, Toluca, México, Mexico
  1. Laboratory of Molecular Biology, Medical Sciences Research Center (CICMED), Autonomous University of the State of Mexico (UAEMex), Jesús Carranza 205, Col. Universidad, C.P. 50130, Toluca, México, Mexico
  3. Imaging Services, Maternal–Perinatal Hospital “Mónica Pretelini Sáenz-(HMPMPS), Health Institute of the State of Mexico (ISEM), C.P. 50130, Toluca, México, Mexico
  4. Pathology Services, HMPMP, C.P. 50130, Toluca, México, Mexico
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Human Genetics
  Biochemistry
  Zoology
  Medical Microbiology
  
• 出版者：Springer Netherlands
• ISSN：1573-4927

文摘

Breast cancer is the most frequent neoplasia in women and is responsible for approximately 13.8% of deaths per year for this gender. It has been suggested that JAK2, STAT3, and NF-κB gene expression is involved in this type of cancer. The objective of the present study was to determine the effect of bistriazole in these signaling pathways in patients with breast cancer and benign mammary lesions. The inhibitory concentration 50 of bistriazole was calculated in cell cultures of patients with benign lesions, Probit = 4.6 μM with IC = 95%. The study was performed by examining 63 women who submitted to mammary biopsies. Biopsies of the mammary lesions were performed, gene expression was determined, and cells were cultured in the presence of 4.6 μM bistriazole. We found that breast cancer is related to age greater than 50 (P ?nbsp;0.01), being overweight (P ?nbsp;0.023) and having a waist circumference larger than 80 cm (P ?nbsp;0.01). The gene expression of JAK2, STAT3, and NF-κB was higher in groups of patients with breast cancer, while SOCS3 expression was lower. After being exposed to bistriazole, the expression of JAK2 and STAT3 decreased, and the expression of SOCS3 and NF-κB increased. In conclusion, this molecule in development has an effect on the gene expression of JAK3 and STAT3; nevertheless, the lack of change in NF-κB indicates that it is not a regulator of inflammation, and therefore, more studies should be performed. Keywords Breast cancer JAK2 NF-κB SOCS3 STAT3