The Combination of Genistein and Imatinib has an Increased Effect on Cell Proliferation Inhibition in Philadelphia Positive Leukemia Cell Lines
-
Ebrahim Azizi
,
Alireza Biglari
,
Ali Abolhassani
,
Saeid Amanpour
,
Samad Muhammadnejad
,
Mahnaz Haddadi
,
Mojtaba Saffari
,
Ali Eslamifar
,
Reza Shirkoohi
Abstract
Background: This study investigated the possible role of Genistein as a combination with Imatinib in controlling leukemia cell line proliferation.Methods: Three cell lines, K562, Kcl22, and CCRF, were cultured and analyzed for MTT, LDH, apoptosis, and cycle cell gene expression in the presence of different dosages of Imatinib and Genistein in combination or separately.Results: Data has shown a decrease in proliferation and an increase in apoptosis activity during combination treatment. LDH assay has shown no additional toxicity due to Genistein consumption in combination therapy. Analysis of the expression of responsible genes for cell cycle demonstrated both G1 (p53, p21 upregulation) andG2 (cdc25c downregulation) inhibitory effect in combination treatment.Conclusion: Altogether, this study suggests thatthe combination treatment of Imatinib and Genistein for leukemia cells resistant to Imatinib can increase treatment efficiency.
1. Pokharel M. Leukemia: A Review Article. IJARPB. 2012;1(3):397- 407.
2. Yang J, Schiffer C. Genetic Biomarkers in Acute Myeloid Leukemia. Expert Review of Hematology. 2012;5(4):395-407.
3. Gonon-Demoulian R, Goldman JM, Nicolini FE. [History of chronic myeloid leukemia: a paradigm in the treatment of cancer]. Bull Cancer. 2014 Jan 1;101(1):56-67.
4. Langie SA, Koppen G, Desaulniers D, Al-Mulla F, Al-Temaimi R, Amedei A, et al. Causes of genome instability: the effect of low dose chemical exposures in modern society. Carcinogenesis. 2015 Jun;36 Suppl 1:S61-88.
5. Ma L, Shan Y, Bai R, Xue L, Eide CA, Ou J, et al. A therapeutically targetable mechanism of BCR-ABL-independent imatinib resistance in chronic myeloid leukemia. Science translational medicine. 2014 Sep 3;6(252):252ra121.
6. Gustafson D, Fish JE, Lipton JH, Aghel N. Mechanisms of Cardiovascular Toxicity of BCR-ABL1 Tyrosine Kinase Inhibitors in Chronic Myelogenous Leukemia. Curr Hematol Malig Rep. 2020 Feb;15(1):20-30.
7. O›Hare T, Deininger M, Eide C, Clackson T, Druker B. Targeting the BCR-ABL signaling pathway in therapy-resistant Philadelphia chromosome-positive leukemia. Clin Cancer Res. 2011;17(2):212-21.
8. Hochhaus A, O›Brien S, Guilhot F, Druker B, Branford S, Foro ni L, et al. Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia. 2009;23(6):1054-61.
9. Siveen KS, Prabhu KS, Achkar IW, Kuttikrishnan S, Shyam S, Khan AQ, et al. Role of Non Receptor Tyrosine Kinases in Hematological Malignances and its Targeting by Natural Products. Molecular cancer. 2018 Feb 19;17(1):31.
10. Rizzo G, Baroni L. Soy, Soy Foods and Their Role in Vegetarian Diets. Nutrients. 2018 Jan 5;10(1).
11. Zhang H, Gordon R, Li W, Yang X, Pattanayak A, Fowler G, et al. Genistein treatment duration effects biomarkers of cell motility in human prostate. PLoS One. 2019;14(3):e0214078.
12. Dong X, Xu W, Sikes RA, Wu C. Combination of low dose of genistein and daidzein has synergistic preventive effects on isogenic human prostate cancer cells when compared with individual soy isoflavone. Food Chem. 2013 Dec 1;141(3):1923-33.
13. Roy Choudhury S, Karmakar S, Banik N, Ray S. Synergistic efficacy of sorafenib and genistein in growth inhibition by down regulating angiogenic and survival factors and increasing apoptosis through upregulation of p53 and p21 in malignant neuroblastoma cells having N-Myc amplification or non-amplification. Invest New Drugs. 2010;28(6):812-24.
14. Privat M, Aubel C, Arnould S, Communal Y, Ferrara M, Bignon Y. AKT and p21 WAF1/CIP1 as potential genistein targets in BRCA1-mutant human breast cancer cell lines. Anticancer Res. 2010;30(6):2049-54.
15. Ratovitski EA. Anticancer Natural Compounds as Epigenetic Modulators of Gene Expression. Current genomics. 2017 Apr;18(2):175-205.
16. Kim SH, Kim CW, Jeon SY, Go RE, Hwang KA, Choi KC. Chemopreventive and chemotherapeutic effects of genistein, a soy isoflavone, upon cancer development and progression in preclinical animal models. Laboratory animal research. 2014 Dec;30(4):143-50.
17. Ismail I, Kang K, Kim J, Sohn Y. Genistein induces G2/M cell cycle arrest and apoptosis in rat neuroblastoma B35 cells; involvement of p21waf1/cip1, Bax and Bcl-2. Korean J Pathol. 2006;40(5):339-47.
18. Bouitbir J, Panajatovic MV, Frechard T, Roos NJ, Krahenbuhl S. Imatinib and Dasatinib Provoke Mitochondrial Dysfunction Leading to Oxidative Stress in C2C12 Myotubes and Human RD Cells. Front Pharmacol. 2020;11:1106.
19. Popow-Wozniak A, Wozniakowska A, Kaczmarek L, Malicka-Blaszkiewicz M, Nowak D. Apoptotic effect of imatinib on human colon adenocarcinoma cells: influence on actin cytoskeleton organization and cell migration. Eur J Pharmacol. 2011 Sep 30;667(1-3):66-73.
20. Eadie LN, Hughes TP, White DL. ABCB1 Overexpression Is a Key Initiator of Resistance to Tyrosine Kinase Inhibitors in CML Cell Lines. PLoS One. 2016;11(8):e0161470.
21. Seo Y, Kim B, Chun S, Park Y, Kang K, Kwon, TG,. Appoptotic effect of genistein , Biochanin A and Apigenin on LNCap and Pc3 cells by P21 through transcriptional inhibition of Polo-Like Kinase1. J KOREAN Med sci. 2011;26(11):1489-94.
22. Erguven M, Karakulak T, Diril MK, Karaca E. How Far Are We from the Rapid Prediction of Drug Resistance Arising Due to Kinase Mutations? ACS Omega. 2021 Jan 19;6(2):1254-65.
23. Majid S, Kikuno N, Nelles J, Noonan E, Tanaka Y, Kawamoto K, et al. Suppressor Genes in Prostate Cancer Cells by Epigenetic Genistein Induces the p21WAF1/CIP1 and p16INK4a Tumor Mechanisms Involving Active Chromatin Modification. Cancer Res. 2008;68(8):2736-44.
24. Berner C, Aumüller E, Gnauck A, Nestelberger M, Just A, Haslberger A. Epigenetic control of estrogen receptor expression and tumor suppressor genes is modulated by bioactive food compounds. Annals of Nutrition & Metabolism. 2011;57(3-4):183-9.
25. Beider K, Darash-Yahana M, Blaier O, Koren-Michowitz M, Abraham M, Wald H, et al. Combination of imatinib with CXCR4 antagonist BKT140 overcomes the protective effect of stroma and targets CML in vitro and in vivo. Mol Cancer Ther. 2014 May;13(5):1155-69.
26. Lee Y, Park O. Soybean isoflavone genistein regulates apoptosis through NF-kappaB dependent and independent pathways. Exp Toxicol Pathol. 2013;65(1-2):1-6.
27. Sferrazza G, Corti M, Brusotti G, Pierimarchi P, Temporini C, Serafino A, et al. Nature-derived compounds modulating Wnt/ beta -catenin pathway: a preventive and therapeutic opportunity in neoplastic diseases. Acta Pharm Sin B. 2020 Oct;10(10):1814-34.
28. Mahmoud AM, Yang W, Bosland MC. Soy isoflavones and prostate cancer: a review of molecular mechanisms. The Journal of steroid biochemistry and molecular biology. 2014 Mar;140:116-32.
29. Yan G, Zou F, Dang B, Zhang Y, Yu G, Liu X, et al. Genistein-induced mitotic arrest of gastric cancer cells by downregulating KIF20A, a proteomics study. Proteomics. 2012;12(14):2391-9.
30. Sánchez Y, Amrán D, Fernández C, de Blas E, Aller P. Genistein selectively potentiates arsenic trioxide-induced apoptosis in human leukemia cells via reactive oxygen species generation and activation of reactive oxygen species-inducible protein kinases (p38-MAPK, AMPK). Int J Cancer 2008. 2008;123(5):1205-14.
31. Sampaio MM, Santos MLC, Marques HS, Goncalves VLS, Araujo GRL, Lopes LW, et al. Chronic myeloid leukemia-from the Philadelphia chromosome to specific target drugs: A literature review. World J Clin Oncol. 2021 Feb 24;12(2):69-94.
32. Mahon F, Hayette S, Lagarde V, Belloc F, Turcq B, Nicolini F, et al. Evidence that resistance to nilotinib may be due to BCR-ABL, Pgp, or Src kinase overexpression. Cancer research. 2008;68(23):9809-16.
33. Soverini S, Mancini M, Bavaro L, Cavo M, Martinelli G. Chronic myeloid leukemia: the paradigm of targeting oncogenic tyrosine kinase signaling and counteracting resistance for successful cancer therapy. Molecular cancer. 2018 Feb 19;17(1):49.
34. Pocaly M, Lagarde V, Etienne G, Ribeil J, Claverol S, Bonneu M, et al. Overexpression of the heat-shock protein 70 is associated to imatinib resistance in chronicmyeloid leukemia. Leukemia. 2007;21(1):93- 101.
35. Drullion C, Lagarde V, Gioia R, Legembre P, Priault M, Cardinaud B, et al. Mycophenolic Acid overcomes imatinib and nilotinib resistance of chronic myeloid leukemia cells by apoptosis or a senescent-like cell cycle arrest. Leukemia research and treatment. 2012;2012:861301.
36. Lin YL, Roux B. Computational analysis of the binding specificity of Gleevec to Abl, c-Kit, Lck, and c-Src tyrosine kinases. J Am Chem Soc. 2013 Oct 2;135(39):14741-53.
37. Ferrandiz N, Caraballo J, Albajar M, Gomez-Casares M, LopezJorge C, Blanco R, et al. p21(Cip1) confers resistance to imatinib in human chronic myeloid leukemia cells. Cancer lett. 2010;292(1):133-9.
38. Vologzhanina AV, Ushakov IE, Korlyukov AA. Intermolecular Interactions in Crystal Structures of Imatinib-Containing Com pounds. Int J Mol Sci. 2020 Nov 26;21(23).
39. Khan N, Afaq F, Mukhtar H. Apoptosis by dietary factors: The suicide solution for delaying cancer growth. Carcinogenesis. 2007;28(2):233-9.
2. Yang J, Schiffer C. Genetic Biomarkers in Acute Myeloid Leukemia. Expert Review of Hematology. 2012;5(4):395-407.
3. Gonon-Demoulian R, Goldman JM, Nicolini FE. [History of chronic myeloid leukemia: a paradigm in the treatment of cancer]. Bull Cancer. 2014 Jan 1;101(1):56-67.
4. Langie SA, Koppen G, Desaulniers D, Al-Mulla F, Al-Temaimi R, Amedei A, et al. Causes of genome instability: the effect of low dose chemical exposures in modern society. Carcinogenesis. 2015 Jun;36 Suppl 1:S61-88.
5. Ma L, Shan Y, Bai R, Xue L, Eide CA, Ou J, et al. A therapeutically targetable mechanism of BCR-ABL-independent imatinib resistance in chronic myeloid leukemia. Science translational medicine. 2014 Sep 3;6(252):252ra121.
6. Gustafson D, Fish JE, Lipton JH, Aghel N. Mechanisms of Cardiovascular Toxicity of BCR-ABL1 Tyrosine Kinase Inhibitors in Chronic Myelogenous Leukemia. Curr Hematol Malig Rep. 2020 Feb;15(1):20-30.
7. O›Hare T, Deininger M, Eide C, Clackson T, Druker B. Targeting the BCR-ABL signaling pathway in therapy-resistant Philadelphia chromosome-positive leukemia. Clin Cancer Res. 2011;17(2):212-21.
8. Hochhaus A, O›Brien S, Guilhot F, Druker B, Branford S, Foro ni L, et al. Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia. 2009;23(6):1054-61.
9. Siveen KS, Prabhu KS, Achkar IW, Kuttikrishnan S, Shyam S, Khan AQ, et al. Role of Non Receptor Tyrosine Kinases in Hematological Malignances and its Targeting by Natural Products. Molecular cancer. 2018 Feb 19;17(1):31.
10. Rizzo G, Baroni L. Soy, Soy Foods and Their Role in Vegetarian Diets. Nutrients. 2018 Jan 5;10(1).
11. Zhang H, Gordon R, Li W, Yang X, Pattanayak A, Fowler G, et al. Genistein treatment duration effects biomarkers of cell motility in human prostate. PLoS One. 2019;14(3):e0214078.
12. Dong X, Xu W, Sikes RA, Wu C. Combination of low dose of genistein and daidzein has synergistic preventive effects on isogenic human prostate cancer cells when compared with individual soy isoflavone. Food Chem. 2013 Dec 1;141(3):1923-33.
13. Roy Choudhury S, Karmakar S, Banik N, Ray S. Synergistic efficacy of sorafenib and genistein in growth inhibition by down regulating angiogenic and survival factors and increasing apoptosis through upregulation of p53 and p21 in malignant neuroblastoma cells having N-Myc amplification or non-amplification. Invest New Drugs. 2010;28(6):812-24.
14. Privat M, Aubel C, Arnould S, Communal Y, Ferrara M, Bignon Y. AKT and p21 WAF1/CIP1 as potential genistein targets in BRCA1-mutant human breast cancer cell lines. Anticancer Res. 2010;30(6):2049-54.
15. Ratovitski EA. Anticancer Natural Compounds as Epigenetic Modulators of Gene Expression. Current genomics. 2017 Apr;18(2):175-205.
16. Kim SH, Kim CW, Jeon SY, Go RE, Hwang KA, Choi KC. Chemopreventive and chemotherapeutic effects of genistein, a soy isoflavone, upon cancer development and progression in preclinical animal models. Laboratory animal research. 2014 Dec;30(4):143-50.
17. Ismail I, Kang K, Kim J, Sohn Y. Genistein induces G2/M cell cycle arrest and apoptosis in rat neuroblastoma B35 cells; involvement of p21waf1/cip1, Bax and Bcl-2. Korean J Pathol. 2006;40(5):339-47.
18. Bouitbir J, Panajatovic MV, Frechard T, Roos NJ, Krahenbuhl S. Imatinib and Dasatinib Provoke Mitochondrial Dysfunction Leading to Oxidative Stress in C2C12 Myotubes and Human RD Cells. Front Pharmacol. 2020;11:1106.
19. Popow-Wozniak A, Wozniakowska A, Kaczmarek L, Malicka-Blaszkiewicz M, Nowak D. Apoptotic effect of imatinib on human colon adenocarcinoma cells: influence on actin cytoskeleton organization and cell migration. Eur J Pharmacol. 2011 Sep 30;667(1-3):66-73.
20. Eadie LN, Hughes TP, White DL. ABCB1 Overexpression Is a Key Initiator of Resistance to Tyrosine Kinase Inhibitors in CML Cell Lines. PLoS One. 2016;11(8):e0161470.
21. Seo Y, Kim B, Chun S, Park Y, Kang K, Kwon, TG,. Appoptotic effect of genistein , Biochanin A and Apigenin on LNCap and Pc3 cells by P21 through transcriptional inhibition of Polo-Like Kinase1. J KOREAN Med sci. 2011;26(11):1489-94.
22. Erguven M, Karakulak T, Diril MK, Karaca E. How Far Are We from the Rapid Prediction of Drug Resistance Arising Due to Kinase Mutations? ACS Omega. 2021 Jan 19;6(2):1254-65.
23. Majid S, Kikuno N, Nelles J, Noonan E, Tanaka Y, Kawamoto K, et al. Suppressor Genes in Prostate Cancer Cells by Epigenetic Genistein Induces the p21WAF1/CIP1 and p16INK4a Tumor Mechanisms Involving Active Chromatin Modification. Cancer Res. 2008;68(8):2736-44.
24. Berner C, Aumüller E, Gnauck A, Nestelberger M, Just A, Haslberger A. Epigenetic control of estrogen receptor expression and tumor suppressor genes is modulated by bioactive food compounds. Annals of Nutrition & Metabolism. 2011;57(3-4):183-9.
25. Beider K, Darash-Yahana M, Blaier O, Koren-Michowitz M, Abraham M, Wald H, et al. Combination of imatinib with CXCR4 antagonist BKT140 overcomes the protective effect of stroma and targets CML in vitro and in vivo. Mol Cancer Ther. 2014 May;13(5):1155-69.
26. Lee Y, Park O. Soybean isoflavone genistein regulates apoptosis through NF-kappaB dependent and independent pathways. Exp Toxicol Pathol. 2013;65(1-2):1-6.
27. Sferrazza G, Corti M, Brusotti G, Pierimarchi P, Temporini C, Serafino A, et al. Nature-derived compounds modulating Wnt/ beta -catenin pathway: a preventive and therapeutic opportunity in neoplastic diseases. Acta Pharm Sin B. 2020 Oct;10(10):1814-34.
28. Mahmoud AM, Yang W, Bosland MC. Soy isoflavones and prostate cancer: a review of molecular mechanisms. The Journal of steroid biochemistry and molecular biology. 2014 Mar;140:116-32.
29. Yan G, Zou F, Dang B, Zhang Y, Yu G, Liu X, et al. Genistein-induced mitotic arrest of gastric cancer cells by downregulating KIF20A, a proteomics study. Proteomics. 2012;12(14):2391-9.
30. Sánchez Y, Amrán D, Fernández C, de Blas E, Aller P. Genistein selectively potentiates arsenic trioxide-induced apoptosis in human leukemia cells via reactive oxygen species generation and activation of reactive oxygen species-inducible protein kinases (p38-MAPK, AMPK). Int J Cancer 2008. 2008;123(5):1205-14.
31. Sampaio MM, Santos MLC, Marques HS, Goncalves VLS, Araujo GRL, Lopes LW, et al. Chronic myeloid leukemia-from the Philadelphia chromosome to specific target drugs: A literature review. World J Clin Oncol. 2021 Feb 24;12(2):69-94.
32. Mahon F, Hayette S, Lagarde V, Belloc F, Turcq B, Nicolini F, et al. Evidence that resistance to nilotinib may be due to BCR-ABL, Pgp, or Src kinase overexpression. Cancer research. 2008;68(23):9809-16.
33. Soverini S, Mancini M, Bavaro L, Cavo M, Martinelli G. Chronic myeloid leukemia: the paradigm of targeting oncogenic tyrosine kinase signaling and counteracting resistance for successful cancer therapy. Molecular cancer. 2018 Feb 19;17(1):49.
34. Pocaly M, Lagarde V, Etienne G, Ribeil J, Claverol S, Bonneu M, et al. Overexpression of the heat-shock protein 70 is associated to imatinib resistance in chronicmyeloid leukemia. Leukemia. 2007;21(1):93- 101.
35. Drullion C, Lagarde V, Gioia R, Legembre P, Priault M, Cardinaud B, et al. Mycophenolic Acid overcomes imatinib and nilotinib resistance of chronic myeloid leukemia cells by apoptosis or a senescent-like cell cycle arrest. Leukemia research and treatment. 2012;2012:861301.
36. Lin YL, Roux B. Computational analysis of the binding specificity of Gleevec to Abl, c-Kit, Lck, and c-Src tyrosine kinases. J Am Chem Soc. 2013 Oct 2;135(39):14741-53.
37. Ferrandiz N, Caraballo J, Albajar M, Gomez-Casares M, LopezJorge C, Blanco R, et al. p21(Cip1) confers resistance to imatinib in human chronic myeloid leukemia cells. Cancer lett. 2010;292(1):133-9.
38. Vologzhanina AV, Ushakov IE, Korlyukov AA. Intermolecular Interactions in Crystal Structures of Imatinib-Containing Com pounds. Int J Mol Sci. 2020 Nov 26;21(23).
39. Khan N, Afaq F, Mukhtar H. Apoptosis by dietary factors: The suicide solution for delaying cancer growth. Carcinogenesis. 2007;28(2):233-9.
| Files | ||
| Issue | Vol 13 No 1 (2021) | |
| Section | Original Articles | |
| DOI | https://doi.org/10.18502/bccr.v13i1.8827 | |
| Keywords | ||
| Cell cycle Genistein Imatinib leukemia Philadelphia chromosome | ||
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How to Cite
1.
Azizi E, Biglari A, Abolhassani A, Amanpour S, Muhammadnejad S, Haddadi M, Saffari M, Eslamifar A, Shirkoohi R. The Combination of Genistein and Imatinib has an Increased Effect on Cell Proliferation Inhibition in Philadelphia Positive Leukemia Cell Lines. Basic Clin Cancer Res. 2021;13(1):21-29.
