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Objective: Breast cancer today is the most frequent cancer among women, and the second most common cause of cancer deaths among women. The aim of this study was to synthesize a new benzoxazole derivative, scan it for anti-cancer potential by MTT test using different breast cancer cell lines, and examine its effects on NF-κB and apoptosis-related proteins (APAF-1, cytochrome C, caspase-3, bcl-2) by Real time PCR method.

Material and Method: A newly-synthesized benzoxazole-derived compound was applied to breast cancer cell lines (MDA-MB, MCF-7) and its cytotoxicity was measured quantitatively by MTT test. Later, the level of its effects on NF-κB and apoptosis-related proteins (APAF-1, cytochrome C, caspase-3, bcl-2) were examined by Real time PCR method.

Results: The structure of the compound synthesized in our study (5-AMINO-2-(P-BROMOFENIL-) BENZOKSAZOLÜN) was proved by elemental analysis, IR, 1H NMR and mass spectroscopy analysis methods. When the toxic effects of the application of BTHB on the cell lines was examined by MTT, it had a greater toxic effect on MCF-7 when compared with MDA-MB, and IC50 levels were lower. When the protein was examined in immunohistochemistry with regard to VEGF, eNOS and TUNEL, it was observed that it caused a reduction in VEGF and an increase in eNOS and TUNEL. In the assay of the proteins by Real time PCR, when heterocyclic compounds were added to the MDA-MBA cell line, there was no difference from the control group in Nfkβ, Caspase, Cytochrome C, but Apaf-1, BCL-2 levels are increased compared with the control group. When heterocyclic compounds were added to the MCF-7 cell line, an decrease was shown in the Nfkβ, Caspase, Cytochrome C, Apaf-1, BCL-2 compared to the control group,

Conclusion: It is felt that this newly synthesized heterocyclic compound increases apoptosis by increasing the activation of Apaf-1, BCL-2, and in this way has shown an effect of inhibiting tumor growth in cancer treatment. In addition.



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KOSOVA, F., TEMİZ-ARPACİ, ÖZLEM, TUĞLU, İBRAHİM, ÖLMEZ, E., ÖZDAL KURT, F., & ARI, Z. (2021). THE EFFECTS OF HETEROCYLİC COMPOUNDS İN BREAST CANCER CELLS. Innovat International Journal Of Medical & Pharmaceutical Sciences, 6(5), 15–20. Retrieved from
Original Article(s)


Arı Z, Kosova F. Adipositokinler ve Meme Kanseri. F.Ü. Sağ Bil Derg. 2008;22(6):377-84.

Demirpençe E. Kanserde Moleküler tedavi Hedefi olarak sinyal Ġletim yolları, 21. Ġstanbul: Ulusal Biyokimya Kongresi; 2009.

Ohta T, Kunimasa K, Kobayashi T, Sakamoto M, Kaji K. Propolis suppresses tumor angiogenesis by inducing apoptosis in tube-forming endothelial cells. Biosci Biotechnol Biochem. 2008;72(9):2436-40. doi: 10.1271/bbb.80169, PMID 18776674.

Temiz-Arpaci O, Yildiz I, Ozkan S, Kaynak F, Aki-Sener E, Yalçin I. Synthesis and biological activity of some new benzoxazoles. Eur J Med Chem. 2008;43(7):1423-31. doi: 10.1016/j.ejmech.2007.09.023, PMID 18023934.

Kiessing S, Rockensuess KD, Varga A, Molnar J, Cherepnev G, Aki E, Yalcin I, Lage H, Amaral L; 2010. Composition useful for the Chemosensibiling and Simultaneous Apoptosis Induction of multidrug resistance of Tumor Cells and Bacteria, Comprise Substituteddisiloxane Compound in the Combination With benzoxazole Derivatives. Patent De. doi: 10.2008027361(A1).

ġener E, Yalçın I, Özden S, Özden T, Akın A, Yıldız S. DOĞA. Vol. 11(3); 1987. p. 391-6.

Uluoğlu Ö. Basic pathology. 1990;4. baskı:855-70.

Wittliff JL. Steroid hormone receptors in breast cancer. Cancer. 1984;53(3);Suppl:630-43. doi: 10.1002/1097-0142(19840201)53:3+<630::aid-cncr2820531308>;2-3, PMID 6692266.

Key T, Appleby P, Barnes I, Reeves G, Endogenous Hormones and Breast Cancer Collaborative Group. Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst. 2002;94(8):606-16. doi: 10.1093/jnci/94.8.606, PMID 11959894.

Stephenson GD, Rose DP. Breast cancer and obesity: an update. Nutr Cancer. 2003;45(1):1-16. doi: 10.1207/S15327914NC4501_1, PMID 12791499.

Clayton CC. Effect of certain benzimidazoles and related compounds upon azo dye destruction by liver homogenates(23789). Proc Soc Exp Biol Med. 1958;98:510-2.

Schulze W, Gutsche W, Jungstand W. Zusammenhänge zwischen Chemischer Struktur und Biologischer Wirksamkeit bei Azomethinen mit Sticksofflost-Gruppen am Ehrlich-Ascitestumor der weissen Maus. Arzneim Forsch. 1965;15(10):1235-8.

Bahner CT, Rıves LM, Mcgaha SW, Rutledge D, Ford D, Gooch E, Westberry D, Zıegler D, Zıegler R. Di- andTri-methoxystyryl derivatives of heterocyclic nitrogen compounds. Arzneim Forsch. 1981;31(3):404-6.

Denny WA, Rewcastle GW, Baguley BC. Potential antitumor agents, structure–activity relationships for 2-Phenylbenzimidaxole-4-carboxamides, A new class of minimal DNA-intercalating agents which may not act via topoisomerase II. J Med Chem. 1990a;33(2):814-9. doi: 10.1021/jm00164a054, PMID 2153829.

Denny WA, Turner PM, Atwell GJ, Rewcastle GW, Ferguson LR. Structure–activity relationships for the mutagenic activity of tricyclic intercalating in Salmonella typhimurium. Mutat Res. 1990b;232(2):233-41. doi: 10.1016/0027-5107(90)90129-r, PMID 2215533.16. Sato S, Kajıura T, Mısato N, Takehana K, Kobayashı T, Tsujı T. AJI9561, A new cytotoxic benzoxazole derivative produced by Streptomyces sp. J. Antibio. 2001;54(1):102-4.

Kumar D, Jacob MR, Reynolds MB, Kerwın SM. Synthesis and evaluation of anticancer benzoxazoles and Benimidazoles related to UK-1. Bioorg Med Chem. 2002;10(12):3997-4004. doi: 10.1016/s0968-0896(02)00327-9, PMID 12413851.

Lage H, Akı-Sener E, Yalcın I. High antineoplastic activity of NewHeterocyclic compounds in cancer cells with resistance against classical DNA topoisomerase II-targeting drugs. Int J Cancer. 2006;119(1):213-20. doi: 10.1002/ijc.21792, PMID 16450374.

Varga A, Akı-Sener E, Yalcın I, Temız-Arpacı O, Tekıner-Gulbas B, Cherepnev G, Molnar J. Induction of apoptosis and necrosis by resistance benzazoles and benzoxazines on tumour cell Line MouseLymphoma L5718 Mdr+cells. In Vivo. 2005;19(6):1087-91. PMID 16277027.

Özkaya AB. HCT–116 Kolon kanser hücre Hattında yeĢil çay Etken Maddesi olan (-)-Epigallokatekin–3-gallatın Apoptoz üzerine Etkisinin Ġncelenmesi. Ġzmir. Dokuz Eylül Üniversitesi; 2008.

Kerr JFR, Wyllie AH, Currie AR. Apoptosis: A basic biological phenomenon with wideranging implications in tissue kinetics. Br J Cancer. 1972;26(4):239-57. doi: 10.1038/bjc.1972.33, PMID 4561027.

Adams JM, Cory S. The Bcl–2 apoptotic switch in cancer development and therapy Oncogene. 2007;26(9):1324-37.

Takayama S, Reed JC, Homma S. Heat-shock proteins as regulators of apoptosis. Oncogene. 2003;22(56):9041-7. doi: 10.1038/sj.onc.1207114, PMID 14663482.

Watanapokasin R, Jarinthanan F, Nakamura Y, Sawasjirakij N, Jaratrungtawee A, Suksamrarn S. Effects of α-mangostin on apoptosis induction of human colon cancer. World J Gastroenterol. 2011;17(16):2086-95. doi: 10.3748/wjg.v17.i16.2086, PMID 21547127.

Hsu SC, Lu JH, Kuo CL, Yang JS, Lin MW, Chen GW, Su CC, Lu HF, Chung JG. Crude Extracts of Solanum lyratum Induced cytotoxicity and Apoptosis in a Human Colon adenocarcinoma Cell Line (Colo 205). Anticancer Res. 2008;28(2A):1045-54. PMID 18507053.

Wang X, Guan X, Wang L, Xie L, Liu Q, Yu Z. Effect of recombinant human p53 adenovirus (Ad-p53) combined with EGFR inhibitor gefitinib on the sensitivity of breast cancer MDA-MB-468 cells. Zhonghua Zhong Liu Za Zhi. 2014 Dec;36(12):886-91). PMID 25623760.

Liu L, Li HX, Lv XQ. The mechanism and significance of E-cadherin, anti-apoptosis B-cell lymphoma-2 protein and se-cadherin roles in cancer. J Biol Regul Homeost Agents. 2014 Oct–Dec;28(4):683-91). PMID 25620178.

Díaz GD, Li Q, Dashwood RH. Caspase-8 and apoptosis-inducing factor Mediate a cytochrome c-independent Pathway of Apoptosis in Human Colon Cancer Cells Induced by the Dietary Phytochemical chlorophyllin. Cancer Res. 2003;63(6):1254-61. PMID 12649185.

Manns J, Daubrawa M, Driessen S, Paasch F, Hoffmann N, Löffler A, Lauber K, Dieterle A, Alers S, Iftner T, Schulze-Osthoff K, Stork B, Wesselborg S. Triggering of a novel intrinsic apoptosis pathway by the kinase inhibitor staurosporine: activation of caspase-9 in the absence of Apaf-1. FASEB J. 2011;25(9):3250-61. doi: 10.1096/fj.10-177527, PMID 21659556.

Douglas RG, Reid PB. Thomas G.C. Apoptosis and cancer. Princ Pract Oncol. 1994;1:1-13.31. Watson AJ, Merritt AJ, Jones LS, Askew JN, Anderson E, Becciolini A, Balzi M, Potten CS, Hickman JA. Evidence for reciprocity of Bcl–2 and p53 expression in human colorectal adenomas and carcinomas. Br J Cancer. 1996;73(8):889-95. doi: 10.1038/bjc.1996.178, PMID 8611422.

Liu H, Jıang X, Zhang MW, Pan YF, Yu YX, Zhang SC, Ma XY, Li QL, Chen K. Association of CASP9, CASP10 gene polymorphisms and tea drinking with colorectal cancer risk in the Han Chinese population. J Zhejiang Univ Sci B. 2013;14(1):47-57. doi: 10.1631/jzus.B1200218, PMID 23303631.

Saleh HA, Jacks H. Correlation of bcl-2 oncoprotein immunohistochemical Expressionwith Proliferation Index and Histopathologic Parameters in Colorectal Neoplasia. Pathol Oncol Res. 1999;5:4.

Türktekin M. Kolon kanseri hücre hattında apigenin flavonoidinin apoptoz yolaklı gen ifade edilmesine olan etkilerinin araĢtırılması. Ankara: Gazi Üniversitesi; 2009.

Wright KM, Smith MI, Farrag L, Deshmukh M. Chromatin modification of Apaf-1 restricts the apoptotic pathway in mature neurons. J Cell Biol. 2007;179(5):825-32. doi: 10.1083/jcb.200708086, PMID 18056406.

Liu K, Duanyang Shu D, Song N, Gai Z, Yuan Y, Li J, Li M, Guo S, Peng J, Hong H. The Role of cytochrome c on Apoptosis Induced by Anagrapha falcifera Multiple Nuclear Polyhedrosis Virus in Insect Spodoptera litura Cells. PLOS ONE. 2012;7(8):e40877. [12 screens]. Available from.

Dr. Gilmore T. NF-kB transcription factors Biology Department. Boston University 5 Cummington Mall. Boston; 2012. p. 02215-2406.

Gochman E, Mahajna J, Reznıck AZ. NF-κB Activation by peroxynitrite through IκBα-dependent Phosphorylation versus Nitration in Colon Cancer Cells. Anticancer Res. 2011;31(5):1607-17. PMID 21617217.

Kosova F, Temiz-Arpacı Ö, Tuğlu Ġ, Ölmez E, Kurt FÖ, Kısmalı G, Arı Z, Arısoy M. Antıcancer Effects of A Newly-Synthesızed benzoxazole-Derıved 5-Amıno-2-[P-bromophenyl]-benzoxazole In Breast Cancer Cell Lınes, TUBITAK projesi, TUBITAK no: 113S998, dergiye gönderildi.

Roomi MW, Ivanov V, Kalinovsky T, Niedzwiecki A, Rath M. In vitro and in vivo antitumorigenic activity of a mixture of lysine, proline, ascorbic acid, and green tea extract on human breast cancer lines MDA-MB-231 and MCF-7. Med Oncol. 2005;22(2):129-38. doi: 10.1385/MO:22:2:129, PMID 15965275.

Zhan Y, Zhang Y, Liu C, Zhang J, Smith WW, Wang N, Chen Y, Zheng L, He L. A novel taspine derivative, HMQ1611, inhibits breast cancer cell growth via estrogen receptor α and EGF receptor signaling pathways. Cancer Prev Res. 2012;5(6):864-73. doi: 10.1158/1940-6207.CAPR-11-0575.

Wang Z, Loo WT, Wang N, Chow LW, Wang D, Han F, Zheng X, Chen JP. Effect of Sanguisorba fficinalis L on breast cancer growth and angiogenesis. Expert Opin Ther Targets. 2012 Mar;16;Suppl 1:S79-89. doi: 10.1517/14728222.2011.642371, PMID 22316502.

Hsieh TC, Elangovan S, Wu JM. Differential suppression of proliferation in MCF-7 and MDA-MB-231 breast cancer cells exposed to alpha-, gamma- and delta-tocotrienols is accompanied by altered expression of oxidative stress modulatory enzymes. Anticancer Res. 2010 Oct;30(10):4169-76. PMID 21036737.