New fluorobenzamidine exerts antitumor activity against breast cancer in mice via pro-apoptotic activity
Tóm tắt
Breast cancer is one of the leading causes of cancer-related morbidities. The present study aimed to evaluate the efficacy of bithiophene-fluorobenzamidine (BFB) against breast cancer induced by 7,12-dimethylbenz(a)anthracene (DMBA) in female Swiss mice and reveal the underlining mechanisms. The mice were randomly divided into five groups; control, BFB-treated group, DMBA-treated group, and the last two groups received DMBA then tamoxifen or BFB. BFB reduced the tumor incidence by ~ 88% versus 30% after TAM. DMBA significantly increased the expression of CDK1 and HER2 and reduced the expression of p53, p21 (CDKN1A), ESR-α, and CAS3. BFB caused significant down-regulation of CDK1 and HER2 and upregulation of p53, p21, ESR-α, and CAS3. In the DMBA-treated mice, cancerous cells metastasized to several organs. This was prevented by the administration of BFB. The antimetastatic and proapoptotic activities were confirmed in MCF7 cells in vitro by the wound healing and annexin V assays, respectively. Kaplan–Meier analysis showed that the BFB increased survival. In the DMBA group, tumors showed invasive carcinoma of grade III with central necrosis, polymorphism, mitotic activity, and numerous newly formed ductules, and colloidal mucinous secretions within adenoid cysts. BFB administration restored the normal structure of the mammary glands. Taken together, BFB has antitumor, pro-apoptotic, and anti-metastatic activities against breast cancer in mice and therefore, it merits further investigations.
Tài liệu tham khảo
Anderson BO, Yip CH, Ramsey SD, et al. Breast cancer in limited-resource countries: health care systems and public policy. Breast J. 2006. https://doi.org/10.1111/j.1075-122X.2006.00203.x.
Chung SS, Vadgama JV. Curcumin and epigallocatechin gallate inhibit the cancer stem cell phenotype via down-regulation of STAT3-NFκB signaling. Anticancer Res. 2015;35(1):39–46.
Martin HL, Smith L, Tomlinson DC. Multidrug-resistant breast cancer: current perspectives. Breast Cancer Targets Ther. 2014;6:1–13.
Sas L, Lardon F, Vermeulen PB, et al. The interaction between ER and NFκB in resistance to endocrine therapy. Breast Cancer Res. 2012. https://doi.org/10.1186/bcr3196.
Vogel VG, Costantino JP, Wickerham DL, Cronin WM. Re: Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 2002;94(19):1504.
Abdel-Shafy HI, Mansour MSM. A review on polycyclic aromatic hydrocarbons: source, environmental impact, effect on human health and remediation. Egypt J Pet. 2016;25(1):107–23.
Gao J, Lauer FT, Dunaway S, Burchiel SW. Cytochrome P450 1B1 is required for 7,12-dimethylbenz(a)-anthracene (DMBA) induced spleen cell immunotoxicity. Toxicol Sci. 2005;86(1):68–74.
Liang Y, Hyder SM. Proliferation of endothelial and tumor epithelial cells by progestin-induced vascular endothelial growth factor from human breast cancer cells: paracrine and autocrine effects. Endocrinology. 2005;146(8):3632–41.
Mafuvadze B, Benakanakere I, López Pérez FR, Besch-Williford C, Ellersieck MR, Hyder SM. Apigenin prevents development of medroxyprogesterone acetate-accelerated 7,12-dimethylbenz(a)anthracene-induced mammary tumors in sprague-dawley rats. Cancer Prev Res. 2011;4(8):1316–24.
Benakanakere I, Besch-Williford C, Carroll CE, Hyder SM. Synthetic progestins differentially promote or prevent 7,12-dimethylbenz(a) anthracene-induced mammary tumors in sprague-dawley rats. Cancer Prev Res. 2010;3(9):1157–67.
Hussin WA, Ismail MA, Alzahrani AM, El-Sayed WM. Evaluation of the biological activity of novel monocationic fluoroaryl-2,2′-bichalcophenes and their analogues. Drug Des Devel Ther. 2014;8:963–72.
Ismail MA, Arafa RK, Youssef MM, El-Sayed WM. Anticancer, antioxidant activities, and DNA affinity of novel monocationic bithiophenes and analogues. Drug Des Devel Ther. 2014;8:1659–72.
Ismail MA, Youssef MM, Arafa RK, Al-Shihry SS, El-Sayed WM. Synthesis and antiproliferative activity of monocationic arylthiophene derivatives. Eur J Med Chem. 2017;126:789–98.
Ismail MA, Negm A, Arafa RK, Abdel-Latif E, El-Sayed WM. Anticancer activity, dual prooxidant/antioxidant effect and apoptosis induction profile of new bichalcophene-5-carboxamidines. Eur J Med Chem. 2019;169:76–88.
Aldaz CM, Liao QY, LaBate M, Johnston DA. Medroxyprogesterone acetate accelerates the development and increases the incidence of mouse mammary tumors induced by dimethylbenzanthracene. Carcinogenesis. 1996;17(9):2069–72.
Chen J, Tan KP, Ward WE, Thompson LU. Exposure to flaxseed or its purified lignan during suckling inhibits chemically induced rat mammary tumorigenesis. Exp Biol Med. 2003;228(8):951–8.
Liang CC, Park AY, Guan JL. In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc. 2007;2:329–33.
El Kholy W, Serag H, Zakaria A. The potency of some natural products on dimethyl benz ( A ) antheracene( DMBA ) induced hepatotoxicity in rats. Egypt J Hosp Med. 2013;53(1):1036–48.
Hajjaji N, Couet C, Besson P, Bougnoux P. DHA effect on chemotherapy-induced body weight loss: an exploratory study in a rodent model of mammary tumors. Nutr Cancer. 2012;64(7):1000–7.
Davis L, Kuttan G. Effect of Withania somnifera on DMBA induced carcinogenesis. J Ethnopharmacol. 2001;75(2–3):165–8.
Heidel SM, MacWilliams PS, Baird WM, et al. Cytochrome P4501B1 mediates induction of bone marrow cytotoxicity and preleukemia cells in mice treated with 7,12-dimethylbenz[a]anthracene. Cancer Res. 2000;60(13):3454–60.
Nazarali SA, Narod SA. Tamoxifen for women at high risk of breast cancer. Breast Cancer Targets Ther. 2014;6:29–36.
Chen WR, Jeong SW, Lucroy MD, et al. Induced antitumor immunity against DMBA-4 metastatic mammary tumors in rats using laser immunotherapy. Int J Cancer. 2003;107(6):1053–7.
Plante I, Stewart MKG, Barr K, Allan AL, Laird DW. Cx43 suppresses mammary tumor metastasis to the lung in a Cx43 mutant mouse model of human disease. Oncogene. 2011;30(14):1681–92.
Santa-Maria CA, Nye L, Mutonga MB, Jain S, Gradishar WJ. Management of metastatic HER2-positive breast cancer: where are we and where do we go from here? Oncology. 2016;30(2):148.
Abdel-Rasol M, El-Beih NM, Yahya SMM, Ismail MA, El-Sayed WM. The antitumor activity of a novel fluorobenzamidine against dimethylhydrazine-induced colorectal cancer in rats. Anticancer Agents Med Chem. 2020;20(4):450–63.
Folkman J. Tumor suppression by p53 is mediated in part by the antiangiogenic activity of endostatin and tumstatin. Sci STKE. 2006. https://doi.org/10.1126/stke.3542006pe35.
Cooper GM. Tumor suppressor genes. The cell: a molecular approach. 2nd ed. Sunderland: Sinauer Associates; 2000.
Khazaei M, Akbari Bazm M, Naseri L, Khazaei M. Methods of inducing breast cancer in animal models: a systematic review. World Cancer Res J. 2018;5(4):1–17.
Das SK, Delp CR, Bandyopadhyay AM, Mathiesen M, Baird WM, Baneriee MR. Fate of 7,12-dimethylbenz(a)anthracene in the mouse mammary gland during initiation and promotion stages of carcinogenesis in vitro. Cancer Res. 1989;49(4):920–4.
Gao J, Mitchell LA, Lauer FT, Burchiel SW. p53 and ATM/ATR regulate 7,12-dimethylbenz[a]anthracene-induced immunosuppression. Mol Pharmacol. 2008;73(1):137–46.
Sharma S, Khan N, Sultana S. Effect of Onosma echioides on DMBA/croton oil mediated carcinogenic response, hyperproliferation and oxidative damage in murine skin. Life Sci. 2004;75(20):2391–410.
Ozaki T, Nakagawara A. Role of p53 in cell death and human cancers. Cancers (Basel). 2011;3(1):994–1013.
Senturk E, Manfredi JJ. p53 and cell cycle effects after DNA damage. Methods Mol Biol. 2013;962:49–61.
Yerlikaya A, Okur E, Ulukaya E. The p53-independent induction of apoptosis in breast cancer cells in response to proteasome inhibitor bortezomib. Tumor Biol. 2012;33(5):1385–92.
Shamloo B, Usluer S. P21 in cancer research. Cancers. 2019. https://doi.org/10.3390/cancers11081178.
Olsson M, Zhivotovsky B. Caspases and cancer. Cell Death Differ. 2011;18(9):1441–9.
Enserink JM, Kolodner RD. An overview of Cdk1-controlled targets and processes. Cell Div. 2010. https://doi.org/10.1186/1747-1028-5-11.
Zeweil MM, Sadek KM, Taha NM, El-Sayed Y, Menshawy S. Graviola attenuates DMBA-induced breast cancer possibly through augmenting apoptosis and antioxidant pathway and downregulating estrogen receptors. Environ Sci Pollut Res. 2019;26(15):15209–17.
Slee EA, Adrain C, Martin SJ. Executioner caspase-3, -6, and -7 perform distinct, non-redundant roles during the demolition phase of apoptosis. J Biol Chem. 2001;276(10):7320–6.
Hariri N, Hasteh F, Walavalkar V, Roma AA, Fadare O. Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 testing in breast cancer: assessing the value of repeated centralized testing in excision specimens. Appl Immunohistochem Mol Morphol. 2019;27:1–7.
Schiff R, Osborne CK. New insight into estrogen receptor-α function and its implication for endocrine therapy resistance in breast cancer. Breast Cancer Res. 2005;7(5):205–11.
Lee AV, Cui X, Oesterreich S. Cross-talk among estrogen receptor, epidermal growth factor, and insulin-like growth factor signaling in breast cancer. Clin Cancer Res. 2001;7(12):4429.
Razandi M, Pedram A, Park ST, Levin ER. Proximal events in signaling by plasma membrane estrogen receptors. J Biol Chem. 2003;278(4):2701–12.
Siersbæk R, Kumar S, Carroll JS. Signaling pathways and steroid receptors modulating estrogen receptor α function in breast cancer. Genes Dev. 2018;32(17–18):1141–54.
Gutierrez MC, Detre S, Johnston S, et al. Molecular changes in tamoxifen-resistant breast cancer: Relationship between estrogen receptor, HER-2, and p38 mitogen-activated protein kinase. J Clin Oncol. 2005;23(11):2469–76.
Shou J, Massarweh S, Osborne CK, et al. Mechanisms of tamoxifen resistance: increased estrogen receptor-HER2/neu cross-talk in ER/HER2-positive breast cancer. J Natl Cancer Inst. 2004;96(12):926–35.
Meng S, Tripathy D, Shete S, et al. HER-2 gene amplification can be acquired as breast cancer progresses. Proc Natl Acad Sci USA. 2004;101(25):9393–8.
Benz CC, Scott GK, Sarup JC, et al. Estrogen-dependent, tamoxifen-resistant tumorigenic growth of MCF-7 cells transfected with HER2/neu. Breast Cancer Res Treat. 1992;24(2):85–95.
Platet N, Cathiard AM, Gleizes M, Garcia M. Estrogens and their receptors in breast cancer progression: a dual role in cancer proliferation and invasion. Crit Rev Oncol Hematol. 2004;51(1):55–67.
Lei JT, Gou X, Seker S, Ellis MJ. ESR1 alterations and metastasis in estrogen receptor positive breast cancer. J Cancer Metastasis Treat. 2019. https://doi.org/10.20517/2394-4722.2019.12.
Johnston SRD, Dowsctt M, Smith IE. Special article: Towards a molecular basis for tamoxifen resistance in breast cancer. Ann Oncol. 1992;3(7):503–11.
Ferguson AT, Lapidus RG, Baylin SB, Davidson NE. Demethylation of the estrogen receptor gene in estrogen receptor-negative breast cancer cells can reactivate estrogen receptor gene expression. Cancer Res. 1995;55(11):2279.
Angeline Kirubha SP, Anburajan M, Venkataraman B, Akila R, Sharath D, Raj B. Evaluation of mammary cancer in 7,12-dimethylbenz(a)anthracene-induced wister rats by asymmetrical temperature distribution analysis using thermography: a comparison with serum Cea levels and histopathology. J Biomed Biotechnol. 2012. https://doi.org/10.1155/2012/786417.
Hirota K, Semenza GL. Regulation of angiogenesis by hypoxia-inducible factor 1. Crit Rev Oncol Hematol. 2006;59(1):15–26.
Tabaczar S, Domeradzka K, Czepas J, et al. Anti-tumor potential of nitroxyl derivative Pirolin in the DMBA-induced rat mammary carcinoma model: a comparison with quercetin. Pharmacol Reports. 2015;67(3):527–34.