Middle East Journal of Cancer

Insight into the Role of Phytochemicals in the Treatment of Triple-Negative Breast Cancer

Document Type : Review Article(s)

Authors

Devangkumar Maru
Anmol Kumar

Department of Biotechnology, Atmiya University, Rajkot, India

https://doi.org/10.30476/mejc.2022.91651.1646
Abstract
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer which is characterized by the absence of progesterone receptor, estrogen receptor, and human epidermal growth factor receptor 2, thus, TNBC patient tumour does not respond to the endocrine therapy. TNBC is highly invasive, highly metastatic, and shows poor prognosis, recurrence, and short survival rate. Surgery, chemotherapy, and radiotherapy are now used as treatments. Despite the wide range of treatment choices, the main drawbacks of current therapies include drug resistance, decreased effectiveness, recurrence within 5 years, and a variety of side-effects. A unique targeted approach is therefore desperately required for the treatment of TNBC. Researchers now have fresh perspectives on the tailored strategy for treating TNBC thanks to phytochemicals. Phytochemicals have shown antiproliferative properties in TNBC and also overcome the drawbacks like recurrence, toxicity, adverse effect, and quality of life. This review highlights different phytochemicals and their potential to target signalling pathways and gene expression to induce apoptosis, cell cycle arrest, inhibition of metastasis, and angiogenesis.

Keywords

Triple-negative breast neoplasms
Genetics
Phytochemicals
Chemotherapy
Signalling

How to cite this article:

Maru D, Kumar A. Insight into the role of phytochemicals in the treatment of triple-negative breast cancer. Middle East J Cancer. 2023;14(2):189-203. doi: 10.30476/mejc.2022.91651.1646.

  1. Mattiuzzi C, Lippi G. Current cancer epidemiology. J Epidemiol Glob Health. 2019;9(4):217-22. doi:10.2991/jegh.k.191008.001.
  2. Elsawaf Z, Sinn HP. Triple-negative breast cancer: clinical and histological correlations. Breast Care (Basel). 2011;6(4):273-8. doi: 10.1159/000331643.
  3. Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer. 2007;109(9):1721-8. doi: 10.1002/cncr.22618.
  4. Anders C, Carey LA. Understanding and treating triple-negative breast cancer. Oncology (Williston Park). 2008;22(11):1233-9; discussion 1239-40, 1243.
  5. Singh J, Asad S, Zhang Y, Nock W, Adams E, Damicis A, et al. Aggressive subsets of metastatic triple negative breast cancer. Clin Breast Cancer. 2020;20(1):e20-6. doi: 10.1016/j.clbc.2019.06.012.
  6. Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007;13(15 Pt 1):4429-34. doi: 10.1158/1078-0432.CCR-06-3045.
  7. GonAalves H, Guerra MR, Duarte Cintra JR, Fayer VA, Brum IV, Bustamante Teixeira MT. Survival study of triple-negative and non-triple-negative breast cancer in a Brazilian cohort. Clin Med Insights Oncol. 2018;12:1179554918790563. doi: 10.1177/1179554918790563.
  8. Wang DY, Jiang Z, Ben-David Y, Woodgett JR, Zacksenhaus E. Molecular stratification within triplenegative breast cancer subtypes. Sci Rep. 2019;9(1):19107. doi: 10.1038/s41598-019-55710-w.
  9. Jiagge E, Chitale D, Newman LA. Triple-negative breast cancer, stem cells, and African ancestry. Am J Pathol. 2018;188(2):271-9. doi: 10.1016/j.ajpath.2017.06.020.
  10. Hahnen E, Hauke J, Engel C, Neidhardt G, Rhiem K, Schmutzler RK. Germline mutations in triple-negative breast cancer. Breast Care (Basel). 2017;12(1):15-9. doi: 10.1159/000455999.
  11. Pierobon M, Frankenfeld CL. Obesity as a risk factor for triple-negative breast cancers: a systematic review and meta-analysis. Breast Cancer Res Treat. 2013;137(1):307-14. doi: 10.1007/s10549-012-2339-3.
  12. Rey-Vargas L, Sanabria-Salas MC, Fejerman L, Serrano-Gomez SJ. Risk factors for triple-negative breast cancer among Latina women. Cancer Epidemiol Biomarkers Prev. 2019;28(11):1771-83. doi: 10.1158/1055-9965.EPI-19-0035.
  13. Perry S, Kowalski TL, Chang CH. Quality of life assessment in women with breast cancer: benefits, acceptability and utilization. Health Qual Life Outcomes. 2007;5:24. doi: 10.1186/1477-7525-5-24.
  14. Dogan BE, Turnbull LW. Imaging of triple-negative breast cancer. Ann Oncol Off J Eur Soc Med Oncol. 2012;23 Suppl 6 (Supplement 6):vi23-9. doi:10.1093/annonc/mds191.
  15. Wong RSY. Apoptosis in cancer: from pathogenesis to treatment. J Exp Clin Cancer Res. 2011;30(Supplement 6):87. doi: 10.1186/1756-9966-30-87.
  16. Al-Mahmood S, Sapiezynski J, Garbuzenko OB, Minko T. Metastatic and triple-negative breast cancer: challenges and treatment options. Drug Deliv Transl Res. 2018;8(5):1483-507. doi: 10.1007/s13346-018-0551-3.
  17. Wahba HA, El-Hadaad HA. Current approaches in treatment of triple-negative breast cancer. Cancer Biol Med. 2015;12(2):106-16. doi: 10.7497/j.issn.2095-3941.2015.0030.
  18. de Ruijter TC, Veeck J, de Hoon JPJ, van Engeland M, Tjan-Heijnen VC. Characteristics of triple-negative breast cancer. J Cancer Res Clin Oncol. 2011;137(2):183-92. doi: 10.1007/s00432-010-0957-x.
  19. HHe MY, Rancoule C, Rehailia-Blanchard A, Espenel S, Trone JC, Bernichon E, et al. Radiotherapy in triplenegative breast cancer: Current situation and upcoming strategies. Crit Rev Oncol Hematol. 2018;131:96-101. doi: 10.1016/j.critrevonc.2018.09.004.
  20. Nedeljković M, Damjanović A. Mechanisms of Chemotherapy resistance in triple-negative breast cancer-how we can rise to the challenge. Cells. 2019; 8(9):957. doi: 10.3390/cells8090957.
  21. Yagata H, Kajiura Y, Yamauchi H. Current strategy for triple-negative breast cancer: appropriate combination of surgery, radiation, and chemotherapy. Breast Cancer. 2011;18(3):165-73. doi: 10.1007/s12282-011-0254-9.
  22. AndrE F, Zielinski CC. Optimal strategies for the treatment of metastatic triple-negative breast cancer with currently approved agents. Ann Oncol Off J Eur Soc Med Oncol. 2012;23 Suppl 6(6):vi46-51. doi:10.1093/annonc/mds195.
  23. Israel BB, Tilghman SL, Parker-Lemieux K, Payton-Stewart F. Phytochemicals: Current strategies for treating breast cancer. Oncol Lett. 2018;15(5):7471-8. doi: 10.3892/ol.2018.8304.
  24. Shahi Thakuri P, Gupta M, Singh S, Joshi R, Glasgow E, Lekan A, et al. Phytochemicals inhibit migration of triple negative breast cancer cells by targeting kinase signalling. BMC Cancer. 2020;20(1):4. doi:10.1186/s12885-019-6479-2.
  25. GrandEr D. How do mutated oncogenes and tumour suppressor genes cause cancer? Med Oncol. 1998;15(1):20-6. doi: 10.1007/BF02787340.
  26. Dixon K, Kopras E. Genetic alterations and DNA repair in human carcinogenesis. Semin Cancer Biol. 2004;14(6):441-8. doi: 10.1016/j.semcancer.2004.06.007.
  27. Shimelis H, LaDuca H, Hu C, Hart SN, Na J, Thomas A, et al. Triple-negative breast cancer risk genes identified by multigene hereditary cancer panel testing. J Natl Cancer Inst. 2018;110(8):855-62. doi:10.1093/jnci/djy106.
  28. Buys SS, Sandbach JF, Gammon A, Patel G, Kidd J, Brown KL, et al. A study of over 35,000 women with breast cancer tested with a 25-gene panel of hereditary cancer genes. Cancer. 2017;123(10):1721-30. doi:10.1002/cncr.30498.
  29. Domagala P, Hybiak J, Cybulski C, Lubinski J. BRCA1/2-negative hereditary triple-negative breast cancers exhibit BRCAness. Int J cancer. 2017;140(7):1545-50. doi: 10.1002/ijc.30570.
  30. Grimmond SM, Palmer JM, Walters MK, Scott C, Nancarrow DJ, Teh BT, et al. Confirmation of susceptibility locus on chromosome 13 in Australian breast cancer families. Hum Genet. 1996;98(1):80-5. doi: 10.1007/s004390050164.
  31. Roy R, Chun J, Powell SN. BRCA1 and BRCA2: different roles in a common pathway of genome protection. Nat Rev Cancer. 2011;12(1):68-78. doi:10.1038/nrc3181.
  32. Newman LA, Reis-Filho JS, Morrow M, Carey LA, King TA. The 2014 Society of Surgical Oncology Susan G. Komen for the Cure Symposium: triple negative breast cancer. Ann Surg Oncol. 2015;22(3): 874-82. doi: 10.1245/s10434-014-4279-0.
  33. Mehrgou A, Akouchekian M. The importance of BRCA1 and BRCA2 genes mutations in breast cancer development. Med J Islam Repub Iran. 2016;30(1):369.
  34. Fostira F, Tsitlaidou M, Papadimitriou C, Pertesi M, Timotheadou E, Stavropoulou AV, et al. Prevalence of BRCA1 mutations among 403 women with triple negative breast cancer: implications for genetic screening selection criteria: a Hellenic Cooperative Oncology Group Study. Breast Cancer Res Treat. 2012;134(1):353-62. doi: 10.1007/s10549-012-2021-9.
  35. Couch FJ, Hart SN, Sharma P, Toland AE, Wang X, Miron P, et al. Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer. J Clin Oncol. 2015;33(4):304-11. doi:10.1200/JCO.2014.57.1414.
  36. Zannini L, Delia D, Buscemi G. CHK2 kinase in the DNA damage response and beyond. J Mol Cell Biol. 2014;6(6):442-57. doi: 10.1093/jmcb/mju045.
  37. Kleiblova P, Stolařova L, Křižova K, Lhota F, Hojny J, Zemankova P, et al. Germline CHEK2 gene mutations in hereditary breast cancer predisposition -Mutation types and their biological and clinical relevance. Klin Onkol. 2019;32 (Supplementum2):36-50. doi: 10.14735/amko2019S36.
  38. Luo L, Gao W, Wang J, Wang D, Peng X, Jia Z, et al. Study on the mechanism of cell cycle checkpoint kinase 2 (CHEK2) gene dysfunction in chemotherapeutic drug resistance of triple negative breast cancer cells. Med Sci Monit. 2018;24:3176-83. doi:10.12659/MSM.907256.
  39. MarEchal A, Zou L. DNA damage sensing by the ATM and ATR kinases. Cold Spring Harb Perspect Biol. 2013;5(9):1-17. doi: 10.1101/cshperspect.a012716.
  40. Domagala P, Jakubowska A, Jaworska-Bieniek K, Kaczmarek K, Durda K, Kurlapska A, et al. Prevalence of germline mutations in genes engaged in DNA damage repair by homologous recombination in patients with triple-negative and hereditary non-triple negative breast cancers. PLoS One. 2015;10(6):e0130393. doi: 10.1371/journal.pone.0130393.
  41. Xia B, Sheng Q, Nakanishi K, Ohashi A, Wu J, Christ N, et al. Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2. Mol Cell. 2006;22(6):719-29. doi: 10.1016/j.molcel.2006.05.022.
  42. Heikkinen T, Karkkainen H, Aaltonen K, Milne RL, Heikkila P, Aittomaki K, et al. The breast cancer susceptibility mutation PALB2 1592delT is associated with an aggressive tumour phenotype. Clin Cancer Res. 2009;15(9):3214-22. doi: 10.1158/1078-0432.CCR-08-3128.
  43. Wiegmans AP, Miranda M, Wen SW, Al-Ejeh F, Moller A. RAD51 inhibition in triple negative breast cancer cells is challenged by compensatory survival signaling and requires rational combination therapy. Oncotarget. 2016;7(37):60087-100. doi: 10.18632/oncotarget.11065.
  44. Smolarz B, Zadrożny M, Duda-Szymańska J, Makowska M, Samulak D, Michalska MM, et al. RAD51 genotype and triple-negative breast cancer (TNBC) risk in Polish women. Pol J Pathol. 2013;64(1):39-43. doi: 10.5114/pjp.2013.34602.
  45. Michalska MM, Samulak D, Romanowicz H, Smolarz B. Single nucleotide polymorphisms (SNPs) of RAD51-G172T and XRCC2-41657C/T homologous recombination repair genes and the risk of triplenegative breast cancer in Polish women. Pathol Oncol Res. 2015;21(4):935-40. doi: 10.1007/s12253-015-9922-y.
  46. Wu J, Lu LY, Yu X. The role of BRCA1 in DNA damage response. Protein Cell. 2010;1(2):117-23. doi:10.1007/s13238-010-0010-5.
  47. Chen H, Wu J, Zhang Z, Tang Y, Li X, Liu S, et al. Association between BRCA status and triple-negative breast cancer: a meta-analysis. Front Pharmacol. 2018;9:909. doi: 10.3389/fphar.2018.00909.
  48. Lee M, Park IA, Heo SH, Kim YA, Gong G, Lee HJ. Association between p53 expression and amount of tumour-infiltrating lymphocytes in triple-negative breast cancer. J Pathol Transl Med. 2019;53(3):180-7. doi: 10.4132/jptm.2019.02.08.
  49. Horigome E, Fujieda M, Handa T, Katayama A, Ito M, Ichihara A, et al. Mutant TP53 modulates metastasis of triple negative breast cancer through adenosine A2b receptor signalling. Oncotarget. 2018;9(77):34554-66. doi: 10.18632/oncotarget.26177.
  50. Li JP, Zhang XM, Zhang Z, Zheng LH, Jindal S, Liu YJ. Association of p53 expression with poor prognosis in patients with triple-negative breast invasive ductal carcinoma. Medicine (Baltimore). 2019;98(18):e15449. doi: 10.1097/MD.0000000000015449.
  51. Na B, Yu X, Withers T, Gilleran J, Yao M, Foo TK, et al. Therapeutic targeting of BRCA1 and TP53 mutant breast cancer through mutant p53 reactivation. NPJ Breast Cancer. 2019;5:14. doi: 10.1038/s41523-019-0110-1.
  52. Khan F, Esnakula A, Ricks-Santi LJ, Zafar R, Kanaan Y, Naab T. Loss of PTEN in high grade advanced stage triple negative breast ductal cancers in African American women. Pathol Res Pract. 2018;214(5):673-8. doi: 10.1016/j.prp.2018.03.020.
  53. Phuah SY, Looi LM, Hassan N, Rhodes A, Dean S, Taib NAM, et al. Triple-negative breast cancer and PTEN (phosphatase and tensin homologue) loss are predictors of BRCA1 germline mutations in women with early-onset and familial breast cancer, but not in women with isolated late-onset breast cancer. Breast Cancer Res. 2012;14(6):R142. doi: 10.1186/bcr3347.
  54. Cossu-Rocca P, Orru S, Muroni MR, Sanges F, Sotgiu G, Ena S, et al. Analysis of PIK3CA mutations and activation pathways in triple negative breast cancer. PLoS One. 2015;10(11):e0141763. doi: 10.1371/journal.pone.0141763.
  55. Mosele F, Stefanovska B, Lusque A, Tran Dien A, Garberis I, Droin N, et al. Outcome and molecular landscape of patients with PIK3CA-mutated metastatic breast cancer. Ann Oncol Off J Eur Soc Med Oncol. 2020;31(3):377-86. doi: 10.1016/j.annonc.2019.11.006.
  56. Ozretic P, Alvir I, Sarcevic B, Vujaskovic Z, Rendic-Miocevic Z, Roguljic A, et al. Apoptosis regulator BCL-2 is an independent prognostic marker for worse overall survival in triple-negative breast cancer patients. Int J Biol Markers. 2018;33(1):109-15. doi:10.5301/ijbm.5000291.
  57. Williams MM, Cook RS. BCL-2 family proteins in breast development and cancer: could Mcl-1 targeting overcome therapeutic resistance? Oncotarget. 2015;6(6):3519-30. doi: 10.18632/oncotarget.2792.
  58. Levva S, Kotoula V, Kostopoulos I, Manousou K, Papadimitriou C, Papadopoulou K, et al. Prognostic evaluation of epidermal growth factor receptor (EGFR) genotype and phenotype parameters in triple-negative breast cancers. Cancer Genomics Proteomics. 2017;14(3):181-95. doi: 10.21873/cgp.20030.
  59. Hashmi AA, Naz S, Hashmi SK, Irfan M, Hussain ZF, Khan EY, et al. Epidermal growth factor receptor (EGFR) overexpression in triple-negative breast cancer: association with clinicopathologic features and prognostic parameters. Surg Exp Pathol. 2019;2(1):6. doi: 10.1186/s42047-018-0029-0.
  60. Zhu X, Zhou W. The emerging regulation of VEGFR-2 in triple-negative breast cancer. Front Endocrinol (Lausanne). 2015;6:159. doi: 10.3389/fendo.2015.00159.
  61. Jafarian AH, Kooshkiforooshani M, Farzad F, Mohamadian Roshan N. The relationship between fibroblastic growth factor receptor-1 (FGFR1) gene amplification in triple negative breast carcinomas and clinicopathological prognostic factors. Iran J Pathol. 2019;14(4):299-304. doi: 10.30699/ijp.2019.96713.1952.
  62. Erber R, Rubner M, Davenport S, Hauke S, Beckmann MW, Hartmann A, et al. Impact of fibroblast growth factor receptor 1 (FGFR1) amplification on the prognosis of breast cancer patients. Breast Cancer Res Treat. 2020;184(2):311-24. doi: 10.1007/s10549-020-05865-2.
  63. Brown AM. Wnt signalling in breast cancer: have we come full circle? Breast Cancer Res. 2001;3(6):351-5. doi: 10.1186/bcr321.
  64. Kucukefe Y, Kaypmaz A. Delayed feedback control as applied to active suspension of a ground vehicle. In: Yasar K, Adnan K, editors. IEEE EUROCON 2009, EUROCON 2009. St. Petersburg: IEEE; 2009. p. 916-21.
  65. Tamai K, Zeng X, Liu C, Zhang X, Harada Y, Chang Z, et al. A mechanism for Wnt coreceptor activation. Mol Cell. 2004;13(1):149-56. doi: 10.1016/s1097-2765(03)00484-2.
  66. Roose J, Molenaar M, Peterson J, Hurenkamp J, Brantjes H, Moerer P, et al. The Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional repressors. Nature. 1998;395(6702):608-12. doi:10.1038/26989.
  67. Sethi JK, Vidal-Puig A. Wnt signalling and the control of cellular metabolism. Biochem J. 2010;427(1):1-17. doi: 10.1042/BJ20091866.
  68. Geyer FC, Lacroix-Triki M, Savage K, Arnedos M, Lambros MB, MacKay A, et al. β-Catenin pathway activation in breast cancer is associated with triple negative phenotype but not with CTNNB1 mutation. Mod Pathol. 2011;24(2):209-31. doi: 10.1038/modpathol.2010.205.
  69. Guo S, Liu M, Gonzalez-Perez RR. Role of Notch and its oncogenic signalling crosstalk in breast cancer. Biochim Biophys Acta. 2011;1815(2):197-213. doi:10.1016/j.bbcan.2010.12.002.
  70. Zhou Y, Xia L, Wang H, Oyang L, Su M, Liu Q, et al. Cancer stem cells in progression of colorectal cancer. Oncotarget. 2018;9(70):33403-15. doi: 10.18632/oncotarget.23607.
  71. Kopan R, Ilagan MXG. The canonical Notch signaling pathway: unfolding the activation mechanism. Cell. 2009;137(2):216-33. doi: 10.1016/j.cell.2009.03.045.
  72. Kontomanolis EN, Kalagasidou S, Pouliliou S, Anthoulaki X, Georgiou N, Papamanolis V, et al. The Notch pathway in breast cancer progression. Scientific World Journal. 2018;2018:2415489. doi: 10.1155/2018/2415489.
  73. Sari IN, Phi LTH, Jun N, Wijaya YT, Lee S, Kwon HY. Hedgehog signalling in cancer: A prospective therapeutic target for eradicating cancer stem cells. Cells. 2018;7(11):1038. doi: 10.3390/cells7110208.
  74. Habib JG, OiShaughnessy JA. The hedgehog pathway in triple-negative breast cancer. Cancer Med. 2016;5(10):2989-3006. doi: 10.1002/cam4.833.
  75. Bhateja P, Cherian M, Majumder S, Ramaswamy B. The Hedgehog signalling pathway: a viable target in breast cancer? Cancers (Basel). 2019;11(8):1126. doi:10.3390/cancers11081126.
  76. Kwon YJ, Hurst DR, Steg AD, Yuan K, Vaidya KS, Welch DR, et al. Gli1 enhances migration and invasion via up-regulation of MMP-11 and promotes metastasis in ERα negative breast cancer cell lines. Clin Exp Metastasis. 2011;28(5):437-49. doi: 10.1007/s10585-011-9382-z.
  77. Harris LG, Pannell LK, Singh S, Samant RS, Shevde LA. Increased vascularity and spontaneous metastasis of breast cancer by hedgehog signalling mediated upregulation of cyr61. Oncogene. 2012;31(28):3370-80. doi: 10.1038/onc.2011.496.
  78. Noman AS, Uddin M, Rahman MZ, Nayeem MJ, Alam SS, Khatun Z, et al. Overexpression of sonic hedgehog in the triple negative breast cancer: clinicopathological characteristics of high burden breast cancer patients from Bangladesh. Sci Rep. 2016; 6:18830. doi: 10.1038/srep18830.
  79. Fresno Vara JA, Casado E, de Castro J, Cejas P, Belda-Iniesta C, Gonzalez-Baron M. PI3K/Akt signaling pathway and cancer. Cancer Treat Rev. 2004;30(2):193-204. doi: 10.1016/j.ctrv.2003.07.007.
  80. Jeong SJ, Dasgupta A, Jung KJ, Um JH, Burke A, Park HU, et al. PI3K/AKT inhibition induces caspase dependent apoptosis in HTLV-1-transformed cells. Virology. 2008;370(2):264-72. doi: 10.1016/j.virol.2007.09.003.
  81. Bender A, Opel D, Naumann I, Kappler R, Friedman L, von Schweinitz D, et al. PI3K inhibitors prime neuroblastoma cells for chemotherapy by shifting the balance towards pro-apoptotic Bcl-2 proteins and enhanced mitochondrial apoptosis. Oncogene. 2011;30(4):494-503. doi: 10.1038/onc.2010.429.
  82. Fend F, Quintanilla-Martinez L. Mantle cell lymphoma. Pathobiology of human disease. Elsevier; 2014. p.1687-700. doi: 10.1016/B978-0-12-386456-7.04107-1.
  83. Zhang W, Liu HT. MAPK signal pathways in the regulation of cell proliferation in mammalian cells. Cell Res. 2002;12(1):9-18. doi: 10.1038/sj.cr.7290105.
  84. Yin L, Duan JJ, Bian XW, Yu S. Triple-negative breast cancer molecular subtyping and treatment progress. Breast Cancer Res. 2020;22(1):61. doi: 10.1186/s13058-020-01296-5.
  85. Widmann C, Gibson S, Jarpe MB, Johnson GL. Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human. Physiol Rev. 1999;79(1):143-80. doi: 10.1152/physrev.1999.79.1.143.
  86. Lee JT, McCubrey JA. The Raf/MEK/ERK signal transduction cascade as a target for chemotherapeutic intervention in leukemia. Leukemia. 2002;16(4):486-507. doi: 10.1038/sj.leu.2402460.
  87. Jiang W, Wang X, Zhang C, Xue L, Yang L. Expression and clinical significance of MAPK and EGFR in triple-negative breast cancer. Oncol Lett. 2020;19(3):1842-8. doi: 10.3892/ol.2020.11274.
  88. Eralp Y, Derin D, Ozluk Y, Yavuz E, Guney N, Saip P, et al. MAPK overexpression is associated with anthracycline resistance and increased risk for recurrence in patients with triple-negative breast cancer. Ann Oncol Off J Eur Soc Med Oncol. 2008;19(4):669-74. doi: 10.1093/annonc/mdm522.
  89. Bartholomeusz C, Gonzalez-Angulo AM, Liu P, Hayashi N, Lluch A, Ferrer-Lozano J, et al. High ERK protein expression levels correlate with shorter survival in triple-negative breast cancer patients. Oncologist. 2012;17(6):766-74. doi: 10.1634/theoncologist.2011-0377.
  90. Gollo AL, Tanobe VOA, de Melo Pereira GV, Marin O, Bonatto SJR, Silva S, et al. Phytochemical analysis and biological activities of in vitro cultured Nidularium procerum, a bromeliad vulnerable to extinction. Sci Rep. 2020;10(1):7008. doi: 10.1038/s41598-020-64026-z.
  91. Cao H, Sethumadhavan K, Bland JM. Isolation of cottonseed extracts that affect human cancer cell growth. Sci Rep. 2018;8(1):10458. doi:10.1038/s41598-018-28773-4.
  92. Messeha SS, Zarmouh NO, Mendonca P, Alwagdani H, Cotton C, Soliman KFA. Effects of gossypol on apoptosis?related gene expression in racially distinct triple-negative breast cancer cells. Oncol Rep. 2019;42(2):467-78. doi: 10.3892/or.2019.7179.
  93. Gilbert NE, O’Reilly JE, Chang CJ, Lin YC, Brueggemeier RW. Antiproliferative activity of gossypol and gossypolone on human breast cancer cells. Life Sci. 1995;57(1):61-7. doi: 10.1016/0024-3205(95)00243-y.
  94. Mishra AP, Salehi B, Sharifi-Rad M, Pezzani R, Kobarfard F, Sharifi-Rad J, et al. Programmed cell death, from a cancer perspective: an overview. Mol Diagn Ther. 2018;22(3):281-95. doi: 10.1007/s40291-018-0329-9.
  95. Liu S, Kulp SK, Sugimoto Y, Jiang J, Chang HL, Dowd MK, et al. The (-)-enantiomer of gossypol possesses higher anticancer potency than racemic gossypol in human breast cancer. Anticancer Res. 2002;22(1A):33-8.
  96. Kelkel M, Schumacher M, Dicato M, Diederich M. Antioxidant and anti-proliferative properties of lycopene. Free Radic Res. 2011;45(8):925-40. doi:10.3109/10715762.2011.564168.
  97. Gloria NF, Soares N, Brand C, Oliveira FL, Borojevic R, Teodoro AJ. Lycopene and beta-carotene induce cell-cycle arrest and apoptosis in human breast cancer cell lines. Anticancer Res. 2014;34(3):1377-86.
  98. Trejo-Solis C, Pedraza-Chaverri J, Torres-Ramos M, Jimenez-Farfan D, Cruz Salgado A, Serrano-Garcia N, et al. Multiple molecular and cellular mechanisms of action of lycopene in cancer inhibition. Evid Based Complement Alternat Med. 2013;2013(I):705121. doi:10.1155/2013/705121.
  99. Takeshima M, Ono M, Higuchi T, Chen C, Hara T, Nakano S. Anti-proliferative and apoptosis-inducing activity of lycopene against three subtypes of human breast cancer cell lines. Cancer Sci. 2014;105(3):252-7. doi: 10.1111/cas.12349.
  100. Strimpakos AS, Sharma RA. Curcumin: preventive and therapeutic properties in laboratory studies and clinical trials. Antioxid Redox Signal. 2008;10(3):511-45. doi: 10.1089/ars.2007.1769.
  101. Sun XD, Liu XE, Huang DS. Curcumin induces apoptosis of triple-negative breast cancer cells by inhibition of EGFR expression. Mol Med Rep. 2012;6(6):1267-70. doi: 10.3892/mmr.2012.1103.
  102. Maiello MR, D’Alessio A, Bevilacqua S, Gallo M, Normanno N, De Luca A. EGFR and MEK blockade in triple negative breast cancer cells. J Cell Biochem. 2015;116(12):2778-85. doi: 10.1002/jcb.25220.
  103. Mimeault M, Batra SK. Potential applications of curcumin and its novel synthetic analogs and nanotechnology-based formulations in cancer prevention and therapy. Chin Med. 2011;6:31. doi:10.1186/1749-8546-6-31.
  104. Hajime Hirose, Hideshi Ishii, Koshi Mimori, Daisuke Ohta, Masahisa Ohkuma, Hirohiko Tsujii, et al. Notch pathway as candidate therapeutic target in Her2/Neu/ErbB2 receptor-negative breast tumours. Oncol Rep. 2010;23(1):35-43. doi: 10.3892/or.
  105. Křižova L, Dadakova K, Kašparovska J, Kašparovsky T. Isoflavones. Molecules. 2019;24(6):1076. doi:10.3390/molecules24061076.
  106. Banerjee S, Li Y, Wang Z, Sarkar FH. Multi-targeted therapy of cancer by genistein. Cancer Lett. 2008;269(2):226-42. doi: 10.1016/j.canlet.2008.03.052.

107.Wu AH, Koh WP, Wang R, Lee HP, Yu MC. Soy intake and breast cancer risk in Singapore Chinese Health Study. Br J Cancer. 2008;99(1):196-200. doi:10.1038/sj.bjc.6604448.

  1. Pan H, Zhou W, He W, Liu X, Ding Q, Ling L, et al. Genistein inhibits MDA-MB-231 triple-negative breast cancer cell growth by inhibiting NF-κB activity via the Notch-1 pathway. Int J Mol Med. 2012;30(2):337-43. doi: 10.3892/ijmm.2012.990.
  2. Donovan MG, Selmin OI, Doetschman TC, Romagnolo DF. Epigenetic activation of BRCA1 by genistein in vivo and triple negative breast cancer cells linked to antagonism toward aryl hydrocarbon receptor. Nutrients. 2019;11(11):2559. doi:10.3390/nu11112559.
  3. Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35(4):495n516. doi:10.1080/01926230701320337.
  4. Sultan AS, Khalil MIM, Sami BM, Alkhuriji AF, Sadek O. Quercetin induces apoptosis in triple-negative breast cancer cells via inhibiting fatty acid synthase and β-catenin. Int J Clin Exp Pathol. 2017;10(1):156-72.
  5. Papaliagkas V, Anogianaki A, Anogianakis G, Ilonidis G. The proteins and the mechanisms of apoptosis: a mini-review of the fundamentals. Hippokratia. 2007;11(3):108-13.
  6. Lin D, Kuang G, Wan J, Zhang X, Li H, Gong X, et al. Luteolin suppresses the metastasis of triple-negative breast cancer by reversing epithelial-to-mesenchymal transition via downregulation of β-catenin expression. Oncol Rep. 2017;37(2):895-902. doi: 10.3892/or.2016.5311.
  7. Huang L, Jin K, Lan H. Luteolin inhibits cell cycle progression and induces apoptosis of breast cancer cells through downregulation of human telomerase reverse transcriptase. Oncol Lett. 2019;17(4):3842-50. doi: 10.3892/ol.2019.10052.
  8. Li J, Gong X, Jiang R, Lin D, Zhou T, Zhang A, et al. Fisetin inhibited growth and metastasis of triplenegative breast cancer by reversing epithelial-to-mesenchymal transition via PTEN/Akt/GSK3β signal pathway. Front Pharmacol. 2018;9:772. doi: 10.3389/fphar.2018.00772.
  9. Smith ML, Murphy K, Doucette CD, Greenshields AL, Hoskin DW. The dietary flavonoid fisetin causes cell cycle arrest, caspase-dependent apoptosis, and enhanced cytotoxicity of chemotherapeutic drugs in triple-negative breast cancer cells. J Cell Biochem. 2016;117(8):1913-25. doi: 10.1002/jcb.25490.
  10. Shindikar A, Singh A, Nobre M, Kirolikar S. Curcumin and resveratrol as promising natural remedies with nanomedicine approach for the effective treatment of triple negative breast cancer. J Oncol. 2016;2016:9750785. doi: 10.1155/2016/9750785.
  11. Horgan XJ, Tatum H, Brannan E, Paull DH, Rhodes LV. Resveratrol analogues surprisingly effective against triple-negative breast cancer, independent of ERα. Oncol Rep. 2019;41(6):3517-26. doi:10.3892/or.2019.7122.
  12. Alasmari MM, Alshaeri HK, Alashari RA, Bohlke M, Maher T, Pino-Figueroa A. Study the effects of capsaicin on triple negative breast cancer cells. J Clin Exp Pathol. 2018;8.
  13. De Santi M, Galluzzi L, Lucarini S, Paoletti MF, Fraternale A, Duranti A, et al. The indole-3-carbinol cyclic tetrameric derivative CTet inhibits cell proliferation via overexpression of p21/CDKN1A in both estrogen receptor-positive and triple-negative breast cancer cell lines. Breast Cancer Res. 2011;13(2):R33. doi: 10.1186/bcr2855.
  14. Elsayed HE, Ebrahim HY, Mohyeldin MM, Siddique AB, Kamal AM, Haggag EG, et al. Rutin as a novel c-Met inhibitory lead for the control of triple negative breast malignancies. Nutr Cancer. 2016;69(8):1256-71. doi: 10.1080/01635581.2017.1367936.
  15. Messeha SS, Zarmouh NO, Asiri A, Soliman KFAA. Rosmarinic acid-induced apoptosis and cell cycle arrest in triple-negative breast cancer cells. Eur J Pharmacol. 2020;885:173419. doi: 10.1016/j.ejphar.2020.173419.
  16. Li YW, Xu J, Zhu GY, Huang ZJ, Lu Y, Li XQ, et al. Apigenin suppresses the stem cell-like properties of triple-negative breast cancer cells by inhibiting YAP/TAZ activity. Cell Death Discov. 2018;4(1):105. doi: 10.1038/s41420-018-0124-8.
  17. Bauer D, Mazzio E, Hilliard A, Oriaku ET, Soliman KFA. Effect of apigenin on whole transcriptome profile of TNFα-activated MDA-MB-468 triple negative breast cancer cells. Oncol Lett. 2020;19(3):2123-32. doi: 10.3892/ol.2020.11327.
  18. Elkhalifa D, Alali F, Al Moustafa AE, Khalil A. Targeting triple negative breast cancer heterogeneity with chalcones: a molecular insight. J Drug Target. 2019;27(8):830-8. doi: 10.1080/1061186X.2018.1561889.
  19. Oh YJ, Seo YH. A novel chalcone-based molecule, BDP inhibits MDA-MB-231 triple-negative breast cancer cell growth by suppressing Hsp90 function. Oncol Rep. 2017;38(4):2343-50. doi: 10.3892/or.2017.5925.
  20. Greenshields AL, Doucette CD, Sutton KM, Madera L, Annan H, Yaffe PB, et al. Piperine inhibits the growth and motility of triple-negative breast cancer cells. Cancer Lett. 2015;357(1):129-40. doi:10.1016/j.canlet.2014.11.017.
  21. Burande AS, Viswanadh MK, Jha A, Mehata AK, Shaik A, Agrawal N, et al. EGFR targeted paclitaxel and piperine co-loaded liposomes for the treatment of triple negative breast cancer. AAPS Pharm Sci Tech. 2020;21(5):151. doi: 10.1208/s12249-020-01671-7.
  22. Mehta R, Katta H, Alimirah F, Patel R, Murillo G, Peng X, et al. Deguelin action involves c-Met and EGFR signaling pathways in triple negative breast cancer cells. PLoS One. 2013;8(6):e65113. doi:10.1371/journal.pone.0065113.
  23. Robles AJ, Du L, Cichewicz RH, Mooberry SL. Maximiscin induces DNA damage, activates DNA damage response pathways, and has selective cytotoxic activity against a subtype of triple-negative breast cancer. J Nat Prod. 2016;79(7):1822-7. doi:10.1021/acs.jnatprod.6b00290.
  24. Shao F, Sun H, Deng CX. Potential therapeutic targets of triple-negative breast cancer based on its intrinsic subtype. Oncotarget. 2017;8(42):73329-44. doi:10.18632/oncotarget.20274.
  25. Anand David AV, Arulmoli R, Parasuraman S. Overviews of biological importance of quercetin: a bioactive flavonoid. Pharmacogn Rev. 2016;10(20):84-9. doi: 10.4103/0973-7847.194044.
  26. Vafadar A, Shabaninejad Z, Movahedpour A, Fallahi F, Taghavipour M, Ghasemi Y, et al. Quercetin and cancer: new insights into its therapeutic effects on ovarian cancer cells. Cell Biosci. 2020;10(1):32. doi: 10.1186/s13578-020-00397-0.
  27. Lin Y, Shi R, Wang X, Shen HM. Luteolin, a flavonoid with potential for cancer prevention and therapy. Curr Cancer Drug Targets. 2008;8(7):634-46. doi: 10.2174/156800908786241050.
  28. Abotaleb M, Samuel SM, Varghese E, Varghese S, Kubatka P, Liskova A, et al. Flavonoids in cancer and apoptosis. Cancers (Basel). 2018;11(1):28. doi:10.3390/cancers11010028.

Home

Guide for Authors

Submit Manuscript

Guide for Reviewers

Contact Us