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:: Volume 28, Issue 3 (Scientific Journal of Kurdistan University of Medical Sciences 2023) ::
SJKU 2023, 28(3): 1-12 Back to browse issues page
Amygdalin may potentiate the effects of lapatinib on SK-BR-3 cancer cell death through increasing Bax expression
Bahman Moradi poodeh
Associate Professor, Department of Laboratory Sciences, Lahijan Branch, Islamic Azad University, Lahijan, Iran. , bmoradipoodeh@yahoo.com
Abstract:   (1944 Views)

Background and Aim: : HER-2 Positive breast cancer is one of the aggressive types of cancer and is resistant to chemotherapy drugs such as lapatinib .Amygdalin is a natural compound found in the seeds of fruits such as apricot, peache, apple and almond. In recent years, antitumor effects of amygdalin have been reported in different types of cancer cells. The present study aimed to investigate the cytotoxic effectes of amygdalin in combination with lapatinib, on cell viability and Bax expression in SK-BR-3 breast cancer cell line as a cell line with high expression of HER-2.
Material and Methods: After cell culture we evaluated the survival of SK-BR-3 cells by MTT after 48 hours of treatment with different concentrations of amygdalin and lapatinib alone and in combination. The pre-apoptotic Bax expression level was measured by western blot method.
Results: Amygdalin and lapatinib significantly decreased survival of SK-BR-3 cells in a dose-dependent manner. The simultaneous use of amygdalin with lapatinib showed that amygdalin enhanced the lethal effect of lapatinib. Also, amygdalin at the concentration of 10 mg/ml increased the effects of 200 nM lapatinib on the expression of Bax protein.
Conclusion: This study showed that the amygdalin-lapatinib combination could be effective for breast cancer patients with HER-2 overexpression. However, more studies are recommended to obtain more definitive results.
Keywords: Lapatinib, Amygdalin, Breast cancer, Bax promoter, SK-BR-3 cell line
Full-Text [PDF 763 kb]   (264 Downloads)    
Type of Study: Original Research | Subject: Molecular Medicine and Genetics
Received: 2022/07/31 | Accepted: 2022/11/7 | Published: 2023/07/31
References
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15. Lewińska A, Wróbel K, Błoniarz D, Adamczyk-Grochala J, Wołowiec S, Wnuk M. Lapatinib-and fulvestrant-PAMAM dendrimer conjugates promote apoptosis in chemotherapy-induced senescent breast cancer cells with different receptor status. Biomaterials Advances. 2022;140:213047. [DOI:10.1016/j.bioadv.2022.213047] [PMID]
16. Moradipoodeh B, Jamalan M, Zeinali M, Fereidoonnezhad M, Mohammadzadeh G. In vitro and in silico anticancer activity of amygdalin on the SK-BR-3 human breast cancer cell line. Molecular Biology Reports. 2019;46(6):6361-70. [DOI:10.1007/s11033-019-05080-3] [PMID]
17. Moradipoodeh B, Jamalan M, Zeinali M, Fereidoonnezhad M, Mohammadzadeh G. Specific targeting of HER2-positive human breast carcinoma SK-BR-3 cells by amygdaline-ZHER2 affibody conjugate. Molecular Biology Reports. 2020;47(9):7139-51. [DOI:10.1007/s11033-020-05782-z] [PMID]
18. Chen Y-J, Yeh M-H, Yu M-C, Wei Y-L, Chen W-S, Chen J-Y, et al. Lapatinib-induced NF-kappaB activation sensitizes triple-negative breast cancer cells to proteasome inhibitors. Breast cancer research. 2013;15(6):1-14. [DOI:10.1186/bcr3575] [PMID] []
19. Berretta M, Della Pepa C, Tralongo P, Fulvi A, Martellotta F, Lleshi A, et al. Use of Complementary and Alternative Medicine (CAM) in cancer patients: An Italian multicenter survey. Oncotarget. 2017;8(15):24401. [DOI:10.18632/oncotarget.14224] [PMID] []
20. Liczbiński P, Bukowska B. Molecular mechanism of amygdalin action in vitro: review of the latest research. Immunopharmacology and immunotoxicology. 2018;40(3):212-8. [DOI:10.1080/08923973.2018.1441301] [PMID]
21. Shi J, Chen Q, Xu M, Xia Q, Zheng T, Teng J, et al. Recent updates and future perspectives about amygdalin as a potential anticancer agent: a review. Cancer Medicine. 2019;8(6):3004-11. [DOI:10.1002/cam4.2197] [PMID] []
22. Albogami S, Alnefaie A. Role of Amygdalin in Blocking DNA Replication in Breast Cancer In Vitro. Current Pharmaceutical Biotechnology. 2021;22(12):1612-27. [DOI:10.2174/1389201022666210203123803] [PMID]
23. Seidman A, Hudis C, Pierri MK, Shak S, Paton V, Ashby M, et al. Cardiac dysfunction in the trastuzumab clinical trials experience. Journal of clinical oncology. 2002;20(5):1215-21. [DOI:10.1200/JCO.2002.20.5.1215] [PMID]
24. Rexer BN, Arteaga CL. Intrinsic and acquired resistance to HER2-targeted therapies in HER2 gene-amplified breast cancer: mechanisms and clinical implications. Critical Reviews™ in Oncogenesis. 2012;17.(1) [DOI:10.1615/CritRevOncog.v17.i1.20] [PMID] []
25. Carpenter RL, Lo H-W. Regulation of apoptosis by HER2 in breast cancer. Journal of carcinogenesis & mutagenesis. 2013;2013(Suppl 7).
26. Oliveras-Ferraros C, Vazquez-Martin A, Cufí S, Torres-Garcia VZ, Sauri-Nadal T, Del Barco S, et al. Inhibitor of Apoptosis (IAP) survivin is indispensable for survival of HER2 gene-amplified breast cancer cells with primary resistance to HER1/2-targeted therapies. Biochemical and biophysical research communications. 2011;407(2):412-9. [DOI:10.1016/j.bbrc.2011.03.039] [PMID]
27. Reisfeld RA. The tumor microenvironment: a target for combination therapy of breast cancer. Critical Reviews™ in Oncogenesis. 2013;1(2-1). [DOI:10.1615/CritRevOncog.v18.i1-2.70] [PMID]
28. Núñez C, Capelo JL, Igrejas G, Alfonso A, Botana LM, Lodeiro C. An overview of the effective combination therapies for the treatment of breast cancer. Biomaterials. 2016;97:34-50. [DOI:10.1016/j.biomaterials.2016.04.027] [PMID]
29. Huang H-L, Chen Y-C, Huang Y-C, Yang K-C, Pan HY, Shih S-P, et al. Lapatinib induces autophagy, apoptosis and megakaryocytic differentiation in chronic myelogenous leukemia K562 cells. PloS one. 2011;6(12):e29014. [DOI:10.1371/journal.pone.0029014] [PMID] []
30. Liu L, Greger J, Shi H, Liu Y, Greshock J, Annan R, et al. Novel mechanism of lapatinib resistance in HER2-positive breast tumor cells: activation of AXL. 2009;69(17):6871-8. [DOI:10.1158/0008-5472.CAN-08-4490] [PMID]
31. Putcha GV, Harris CA, Moulder KL, Easton RM, Thompson CB, Johnson Jr EM. Intrinsic and extrinsic pathway signaling during neuronal apoptosis: lessons from the analysis of mutant mice. The Journal of cell biology. 2002;157(3):441-53. [DOI:10.1083/jcb.200110108] [PMID] []
32. Fulda S, Debatin K-M. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene. 2006;25(34):4798-811. [DOI:10.1038/sj.onc.1209608] [PMID]
33. Park H-J, Yoon S-H, Han L-S, Zheng L-T, Jung K-H, Uhm Y-K, et al. Amygdalin inhibits genes related to cell cycle in SNU-C4 human colon cancer cells. World journal of gastroenterology: WJG. 2005;11(33):5156.
34. Nahta R, Yuan LX, Du Y, Esteva FJ. Lapatinib induces apoptosis in trastuzumab-resistant breast cancer cells: effects on insulin-like growth factor I signaling. Molecular cancer therapeutics. 2007;6(2):667-74. [DOI:10.1158/1535-7163.MCT-06-0423] [PMID]
35. Gril B, Palmieri D, Bronder JL, Herring JM, Vega-Valle E, Feigenbaum L, et al. Effect of lapatinib on the outgrowth of metastatic breast cancer cells to the brain. 2008;100(15):1092-103. [DOI:10.1093/jnci/djn216] [PMID] []
36. Guan M, Tong Y, Guan M, Liu X, Wang M, Niu R, et al. Lapatinib inhibits breast cancer cell proliferation by influencing PKM2 expression. 2018;17:1533034617749418. [DOI:10.1177/1533034617749418] [PMID] []
37. Parkin DM. Global cancer statistics in the year 2000. The lancet oncology. 2001;2(9):533-43. [DOI:10.1016/S1470-2045(01)00486-7] [PMID]
38. Miller KD, Nogueira L, Mariotto AB, Rowland JH, Yabroff KR, Alfano CM, et al. Cancer treatment and survivorship statistics, 2019. CA: a cancer journal for clinicians. 2019;69(5):363-85. [DOI:10.3322/caac.21565] [PMID]
39. DeSantis CE, Ma J, Gaudet MM, Newman LA, Miller KD, Goding Sauer A, et al. Breast cancer statistics, 2019. CA: a cancer journal for clinicians. 2019;69(6):438-51. [DOI:10.3322/caac.21583] [PMID]
40. Simpson PT, Reis‐Filho JS, Gale T, Lakhani SR. Molecular evolution of breast cancer. The Journal of Pathology: A Journal of the Pathological Society of Great Britain and Ireland. 2005;205(2):248-54. [DOI:10.1002/path.1691] [PMID]
41. Kittaneh M, Montero AJ, Glück S. Molecular profiling for breast cancer: a comprehensive review. Biomarkers in cancer. 2013;5:BIC. S9455. [DOI:10.4137/BIC.S9455] [PMID] []
42. Park HS, Jang MH, Kim EJ, Kim HJ, Lee HJ, Kim YJ, et al. High EGFR gene copy number predicts poor outcome in triple-negative breast cancer. Modern pathology. 2014;27(9):1212-22. [DOI:10.1038/modpathol.2013.251] [PMID]
43. Park K, Han S, Shin E, Kim H, Kim J. EGFR gene and protein expression in breast cancers. European Journal of Surgical Oncology (EJSO). 2007;33(8):956-60. [DOI:10.1016/j.ejso.2007.01.033] [PMID]
44. Bose R, Kavuri SM, Searleman AC, Shen W, Shen D, Koboldt DC, et al. Activating HER2 mutations in HER2 gene amplification negative breast cancer. Cancer discovery. 2013;3(2):224-37. [DOI:10.1158/2159-8290.CD-12-0349] [PMID] []
45. Seol H, Lee HJ, Choi Y, Lee HE, Kim YJ, Kim JH, et al. Intratumoral heterogeneity of HER2 gene amplification in breast cancer: its clinicopathological significance. Modern pathology. 2012;25(7):938-48. [DOI:10.1038/modpathol.2012.36] [PMID]
46. Meng S, Tripathy D, Shete S, Ashfaq R, Haley B, Perkins S, et al. HER-2 gene amplification can be acquired as breast cancer progresses. Proceedings of the National Academy of Sciences. 2004;101(25):9393-8. [DOI:10.1073/pnas.0402993101] [PMID] []
47. Sledge GW, Mamounas EP, Hortobagyi GN, Burstein HJ, Goodwin PJ, Wolff AC. Past, present, and future challenges in breast cancer treatment. Journal of clinical oncology. 2014;32(19):1979. [DOI:10.1200/JCO.2014.55.4139] [PMID] []
48. Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, De Azambuja E, Aura C, et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. The Lancet. 2012;379(9816):633-40. [DOI:10.1016/S0140-6736(11)61847-3] [PMID]
49. Bundred N, Porta N, Brunt AM, Cramer A, Hanby A, Shaaban AM, et al. Combined Perioperative Lapatinib and Trastuzumab in Early HER2-Positive Breast Cancer Identifies Early Responders: Randomized UK EPHOS-B Trial Long-Term Results. Clinical Cancer Research. 2022;28(7):1323-34. [DOI:10.1158/1078-0432.CCR-21-3177] [PMID] []
50. Liu C, Cheng X, Xing J, Li J, Li Z, Jian D, et al. CIRBP-OGFR axis safeguards against cardiomyocyte apoptosis and cardiotoxicity induced by chemotherapy. International journal of biological sciences. 2022;18(7):2882. [DOI:10.7150/ijbs.69655] [PMID] []
51. Lewińska A, Wróbel K, Błoniarz D, Adamczyk-Grochala J, Wołowiec S, Wnuk M. Lapatinib-and fulvestrant-PAMAM dendrimer conjugates promote apoptosis in chemotherapy-induced senescent breast cancer cells with different receptor status. Biomaterials Advances. 2022;140:213047. [DOI:10.1016/j.bioadv.2022.213047] [PMID]
52. Moradipoodeh B, Jamalan M, Zeinali M, Fereidoonnezhad M, Mohammadzadeh G. In vitro and in silico anticancer activity of amygdalin on the SK-BR-3 human breast cancer cell line. Molecular Biology Reports. 2019;46(6):6361-70. [DOI:10.1007/s11033-019-05080-3] [PMID]
53. Moradipoodeh B, Jamalan M, Zeinali M, Fereidoonnezhad M, Mohammadzadeh G. Specific targeting of HER2-positive human breast carcinoma SK-BR-3 cells by amygdaline-ZHER2 affibody conjugate. Molecular Biology Reports. 2020;47(9):7139-51. [DOI:10.1007/s11033-020-05782-z] [PMID]
54. Chen Y-J, Yeh M-H, Yu M-C, Wei Y-L, Chen W-S, Chen J-Y, et al. Lapatinib-induced NF-kappaB activation sensitizes triple-negative breast cancer cells to proteasome inhibitors. Breast cancer research. 2013;15(6):1-14. [DOI:10.1186/bcr3575] [PMID] []
55. Berretta M, Della Pepa C, Tralongo P, Fulvi A, Martellotta F, Lleshi A, et al. Use of Complementary and Alternative Medicine (CAM) in cancer patients: An Italian multicenter survey. Oncotarget. 2017;8(15):24401. [DOI:10.18632/oncotarget.14224] [PMID] []
56. Liczbiński P, Bukowska B. Molecular mechanism of amygdalin action in vitro: review of the latest research. Immunopharmacology and immunotoxicology. 2018;40(3):212-8. [DOI:10.1080/08923973.2018.1441301] [PMID]
57. Shi J, Chen Q, Xu M, Xia Q, Zheng T, Teng J, et al. Recent updates and future perspectives about amygdalin as a potential anticancer agent: a review. Cancer Medicine. 2019;8(6):3004-11. [DOI:10.1002/cam4.2197] [PMID] []
58. Albogami S, Alnefaie A. Role of Amygdalin in Blocking DNA Replication in Breast Cancer In Vitro. Current Pharmaceutical Biotechnology. 2021;22(12):1612-27. [DOI:10.2174/1389201022666210203123803] [PMID]
59. Seidman A, Hudis C, Pierri MK, Shak S, Paton V, Ashby M, et al. Cardiac dysfunction in the trastuzumab clinical trials experience. Journal of clinical oncology. 2002;20(5):1215-21. [DOI:10.1200/JCO.2002.20.5.1215] [PMID]
60. Rexer BN, Arteaga CL. Intrinsic and acquired resistance to HER2-targeted therapies in HER2 gene-amplified breast cancer: mechanisms and clinical implications. Critical Reviews™ in Oncogenesis. 2012;17.(1) [DOI:10.1615/CritRevOncog.v17.i1.20] [PMID] []
61. Carpenter RL, Lo H-W. Regulation of apoptosis by HER2 in breast cancer. Journal of carcinogenesis & mutagenesis. 2013;2013(Suppl 7).
62. Oliveras-Ferraros C, Vazquez-Martin A, Cufí S, Torres-Garcia VZ, Sauri-Nadal T, Del Barco S, et al. Inhibitor of Apoptosis (IAP) survivin is indispensable for survival of HER2 gene-amplified breast cancer cells with primary resistance to HER1/2-targeted therapies. Biochemical and biophysical research communications. 2011;407(2):412-9. [DOI:10.1016/j.bbrc.2011.03.039] [PMID]
63. Reisfeld RA. The tumor microenvironment: a target for combination therapy of breast cancer. Critical Reviews™ in Oncogenesis. 2013;1(2-1). [DOI:10.1615/CritRevOncog.v18.i1-2.70] [PMID]
64. Núñez C, Capelo JL, Igrejas G, Alfonso A, Botana LM, Lodeiro C. An overview of the effective combination therapies for the treatment of breast cancer. Biomaterials. 2016;97:34-50. [DOI:10.1016/j.biomaterials.2016.04.027] [PMID]
65. Huang H-L, Chen Y-C, Huang Y-C, Yang K-C, Pan HY, Shih S-P, et al. Lapatinib induces autophagy, apoptosis and megakaryocytic differentiation in chronic myelogenous leukemia K562 cells. PloS one. 2011;6(12):e29014. [DOI:10.1371/journal.pone.0029014] [PMID] []
66. Liu L, Greger J, Shi H, Liu Y, Greshock J, Annan R, et al. Novel mechanism of lapatinib resistance in HER2-positive breast tumor cells: activation of AXL. 2009;69(17):6871-8. [DOI:10.1158/0008-5472.CAN-08-4490] [PMID]
67. Putcha GV, Harris CA, Moulder KL, Easton RM, Thompson CB, Johnson Jr EM. Intrinsic and extrinsic pathway signaling during neuronal apoptosis: lessons from the analysis of mutant mice. The Journal of cell biology. 2002;157(3):441-53. [DOI:10.1083/jcb.200110108] [PMID] []
68. Fulda S, Debatin K-M. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene. 2006;25(34):4798-811. [DOI:10.1038/sj.onc.1209608] [PMID]
69. Park H-J, Yoon S-H, Han L-S, Zheng L-T, Jung K-H, Uhm Y-K, et al. Amygdalin inhibits genes related to cell cycle in SNU-C4 human colon cancer cells. World journal of gastroenterology: WJG. 2005;11(33):5156.
70. Nahta R, Yuan LX, Du Y, Esteva FJ. Lapatinib induces apoptosis in trastuzumab-resistant breast cancer cells: effects on insulin-like growth factor I signaling. Molecular cancer therapeutics. 2007;6(2):667-74. [DOI:10.1158/1535-7163.MCT-06-0423] [PMID]
71. Gril B, Palmieri D, Bronder JL, Herring JM, Vega-Valle E, Feigenbaum L, et al. Effect of lapatinib on the outgrowth of metastatic breast cancer cells to the brain. 2008;100(15):1092-103. [DOI:10.1093/jnci/djn216] [PMID] []
72. Guan M, Tong Y, Guan M, Liu X, Wang M, Niu R, et al. Lapatinib inhibits breast cancer cell proliferation by influencing PKM2 expression. 2018;17:1533034617749418. [DOI:10.1177/1533034617749418] [PMID] []
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Moradi poodeh B. Amygdalin may potentiate the effects of lapatinib on SK-BR-3 cancer cell death through increasing Bax expression. SJKU 2023; 28 (3) :1-12
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Volume 28, Issue 3 (Scientific Journal of Kurdistan University of Medical Sciences 2023) Back to browse issues page
مجله علمی دانشگاه علوم پزشکی کردستان Scientific Journal of Kurdistan University of Medical Sciences
مجله علمی دانشگاه علوم پزشکی کردستان Scientific Journal of Kurdistan University of Medical Sciences
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