Middle East Journal of Cancer

Flaxseed Extract Can Modulates Apoptotic Genes to Promote Cell Death in Breast Cancer Cells

Document Type : Original Article(s)

Authors

Ehsan Zare Mehrjardi 1
Shadi Montazerolhojeh 2
Masoud Dehghan Tezerjani 3
Safieh Dehshiri 2
Mahmood Dehghani Ashkezari 2
Seyed Morteza Seifati 2

1 Department of Industrial Environmental and Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran

2 Medical Biotechnology Research Center, Ashkezar Branch, Islamic Azad University, Ashkezar, Yazd, Iran

3 Abortion Research Centre, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

https://doi.org/10.30476/mejc.2024.102754.2108
Abstract
Background: Breast cancer is a multifactorial malignancy with uncertain treatment outcomes, making its treatment challenging. Balanced level of genes expression, including BAX, BCL2L1 (bcl-xl) and BCL-2 are needed to regulate apoptosis pathway in cancers. The aim of this study was to examine the impact of flaxseed extract on the expression of BAX, BCL-2, and BCL2L1 (bcl-xl) gens in BT-474 and MCF-7 breast cancer cells.
Method: This in vitro experimental study investigated the impact of flaxseed extract on apoptosis and the proliferation of BT-474 and MCF-7 breast cancer cells. MTT assay was conducted on flaxseed extract treated BT-474 and MCF-7 cells at concentrations 3.90628, 7.8125, 156.125, 312.5, 125, 2, 1000, and 2000 µg/ml for 24, 48 and 72h. IC50 (μg/ml) was calculated for flaxseed extract in both cells. The expression of BCL2L1 (bcl-xl), bcl-2 and Bax genes were evaluated at these concentrations using real time Polymerase Chain Reaction (PCR). The data from different groups were analyzed using the Student's t-test.
Results: Flaxseed extract reduced the multiplication and growth of BT-474 and MCF-7 cells in a concentration-dependent manner over 24, 48, and 72 hours of incubation. In both flaxseed-extract exposed BT-474 and MCF-7 cell lines, the BAX gene expression increased (P < 0.05); however, the gene expression of BCL2L1 (bcl-xl) and BCL-2 genes decreased (P < 0.05).
Conclusion: Incubating BT-474 and MCF-7 with flaxseed extract repressed their growth and induced apoptosis. These results may provide precious information for developing a plant-based agent to prevent or treat breast cancer.

Highlights

 Ehsan Zare Mehrjardi (PubMed)

Seyed Morteza Seifati (Google Scholar)

Keywords

Breast Neoplasms
Apoptosis
Plant Extracts
IC50
Cell Line
Subjects

How to cite this article:

Zare Mehrjardi E, Montazerolhojeh S, Dehghan Tezerjani M, Dehshiri S, Dehghani Ashkezari M, Seifati SM. Flaxseed Extract Can Modulates Apoptotic Genes to Promote Cell Death in Breast Cancer Cells. Middle East J Cancer. 2025;16(3):258-66 doi: 10.30476/mejc.2024.102754.2108.

 

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. doi: 10.3322/caac.21492. Erratum in: CA Cancer J Clin. 2020;70(4):313. doi: 10.3322/caac.21609. PMID: 30207593.
  2. Kondov B, Milenkovikj Z, Kondov G, Petrushevska G, Basheska N, Bogdanovska-Todorovska M, et al. Presentation of the molecular subtypes of breast cancer detected by immunohistochemistry in surgically treated patients. Open Access Maced J Med Sci. 2018;6(6):961-7. doi: 10.3889/oamjms.2018.231. PMID: 29983785; PMCID: PMC6026408.
  3. Dehghan Tezerjani M, Beik M, Kalantar SM, Rasti A, Kalantar SM, Shiryazdi SM. Transforming growth factor Beta leucine10 proline variation and breast cancer risk in Iranian women. Iran J Public Health. 2015;44(3):427-9. PMID: 25905093; PMCID: PMC4402428.
  4. Makhoul I. Therapeutic strategies for breast cancer. In: Bland, Kirby I.; Copeland, Edward M.; Klimberg, Suzanne, et al., editors. The breast. The 5th ed. Elsevier; 2018. p. 315-30.
  5. Almanghadim HG, Nourollahzadeh Z, Khademi NS, Tezerjani MD, Sehrig FZ, Estelami N, et al. Application of nanoparticles in cancer therapy with an emphasis on cell cycle. Cell Biol Int. 2021;45(10):1989-98. doi: 10.1002/cbin.11658. PMID: 34233087.
  6. Ravi S, Alencar AM Jr, Arakelyan J, Xu W, Stauber R, Wang CI, et al. An Update to hallmarks of cancer. Cureus. 2022;14(5):e24803. doi: 10.7759/cureus.24803. PMID: 35686268; PMCID: PMC9169686.
  7. Krüger M. Remove, refine, reduce: Cell death in biological systems. Int J Mol Sci. 2023; 24(8):7028. doi: 10.3390/ijms24087028. PMID: 37108191; PMCID: PMC10138335.
  8. Shoshan-Barmatz V, Arif T, Shteinfer-Kuzmine A. Apoptotic proteins with non-apoptotic activity: expression and function in cancer. Apoptosis. 2023;28(5-6):730-53. doi: 10.1007/s10495-023-01835-3. PMID: 37014578. PMCID: PMC10071271.
  9. Kaloni D, Diepstraten ST, Strasser A, Kelly GL. BCL-2 protein family: attractive targets for cancer therapy. Apoptosis. 2023;28(1-2):20-38. doi: 10.1007/s10495-022-01780-7. PMID: 36342579. PMCID: PMC9950219.
  10. Janaghard MS, Soleimani S, Movafagh A, Motallebi M, Mousavi SA, Moghadam AAS, et al. Bcl-2 expression in cell lines breast cancer and death program. Cell Mol Biol. 2023;69(14):277-85. doi: 10.14715/cmb/2023.69.14.46. PMID: 38279418.
  11. Keitel U, Scheel AH, Thomale J, Halpape R, Kaulfuß S, Scheel CH, et al. Bcl-xL mediates therapeutic resistance of a mesenchymal breast cancer cell subpopulation. Oncotarget. 2014;5(23):11778-91. doi: 10.18632/oncotarget.2634. PMID: 25473892. PMCID: PMC4322974.
  12. Nocquet L, Roul J, Lefebvre CC, Duarte L, Campone M, Juin PP, et al. Low BCL-xL expression in triple-negative breast cancer cells favors chemotherapy efficacy, and this effect is limited by cancer-associated fibroblasts. Sci Rep. 2024;14:14177. doi: 10.1038/s41598-024-64696-z. PMID: 38898061. PMCID: PMC11187150.
  13. 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. PMID: 25784482. PMCID: PMC4414133.
  14. Khater SI, Shalabi M, Alammash BB, Alrais AI, Al-Ahmadi DS, Alqahtani LS, et al. Evaluation of flaxseed lignan-enriched extract targeting autophagy, apoptosis, and hedgehog pathways against experimentally induced obesity. J Adv Vet Anim Res. 2023;10(2):321-35. doi: 10.5455/javar.2023.j684. PMID: 37534085. PMCID: PMC10390674.
  15. Bera RK, Singh R, Mollah MKI, Mistry A, Ghosh N, Kundu A, et al. Natural products use for the management of breast cancer: A review. Educ Adm Theory Pract. 2024;30(4):2578-92. doi: 10.53555/kuey.v30i4.1899.
  16. Ávila-Gálvez MÁ, Giménez-Bastida JA, Espín JC, González-Sarrías A. Dietary phenolics against breast cancer. A critical evidence-based review and future perspectives. Int J Mol Sci. 2020;21(16):5718. doi: 10.3390/ijms21165718. PMID: 32784973. PMCID: PMC7461055.
  17. Tse TJ, Guo Y, Shim YY, Purdy SK, Kim JH, Cho JY, et al. Availability of bioactive flax lignan from foods and supplements. Crit Rev Food Sci Nutr. 2023;63(29):9843-58.  doi: 10.1080/10408398.2022.2072807. PMID: 35532015.
  18. Özgöçmen M, Bayram D, Yavuz Türel G, Toğay VA, Şahin Calapoğlu N. Secoisolariciresinol diglucoside induces caspase-3-mediated apoptosis in monolayer and spheroid cultures of human colon carcinoma cells. J Food Biochem. 2021;45(5):e13719. doi: https://doi.org/10.1111/jfbc.13719. PMID: 33778961
  19. Bayar İ, Akkoç S. A mini review on components of flax seed and their effects on breast cancer. J Agr Sci. 2024;30(2):205-15. doi: 10.15832/ankutbd.1349777.
  20. Hu T, Linghu K, Huang S, Battino M, Georgiev MI, Zengin G, et al. Flaxseed extract induces apoptosis in human breast cancer MCF-7 cells. Food chem toxicol. 2019;127:188-96. doi: 10.1016/j.fct.2019.03.029. PMID: 30905866.
  21. Mason JK, Fu M, Chen J, Thompson LU. Flaxseed oil enhances the effectiveness of trastuzumab in reducing the growth of HER2-overexpressing human breast tumors (BT-474). J Nutr Biochem. 2015;26(1):16-23. doi: 10.1016/j.jnutbio.2014.08.001. PMID: 25441844
  22. Wiggins AK, Kharotia S, Mason JK, Thompson LU. α-Linolenic acid reduces growth of both triple negative and luminal breast cancer cells in high and low estrogen environments. Nutr Cancer. 2015;67(6):1001-9. doi: 10.1080/01635581.2015.1053496. PMID: 26134471.
  23. Wörmann B. Breast cancer: basics, screening, diagnostics and treatment. Med Monatsschr Pharm. 2017;40(2):55-64. PMID: 29952495.
  24. Khan MM, Yalamarty SSK, Rajmalani BA, Filipczak N, Torchilin VP. Recent strategies to overcome breast cancer resistance. Crit Rev Oncol Hematol. 2024;197:104351. doi: 10.1016/j.critrevonc.2024.104351. PMID: 38615873.
  25. Chimento A, De Luca A, D’Amico M, De Amicis F, Pezzi V. The involvement of natural polyphenols in molecular mechanisms inducing apoptosis in tumor cells: A promising adjuvant in cancer therapy. Int J Mol Sci. 2023;24(2):1680. doi:10.3390/ijms24021680. PMID: 36675194. PMCID: PMC9863215.
  26. Huang W, Guo X, Wang C, Alzhan A, Liu Z, Ma X, Shu Q. α-Linolenic acid induces apoptosis, inhibits the invasion and metastasis, and arrests cell cycle in human breast cancer cells by inhibiting fatty acid synthase. J Func Foods. 2022;92:105041. doi:10.1016/j.jff.2022.105041.
  27. Hu T, Linghu K, Huang S, Battino M, Georgiev MI, Zengin G, et al. Flaxseed extract induces apoptosis in human breast cancer MCF-7 cells. Food Chem Toxicol. 2019;127:188-96. doi: 10.1016/j.fct.2019.03.029. PMID: 30905866.
  28. Mason JK, Thompson LU. Flaxseed and its lignan and oil components: can they play a role in reducing the risk of and improving the treatment of breast cancer?. Appl Physiol Nutr Metab. 2014;39:663-78. doi: 10.1139/apnm-2013-0420. PMID: 24869971.
  29. Mansour E, Abd-Rabou AA, El-Atawy MA, Ahmed HA, El-Farargy AF, Abd El-Mawgoud HK. Induction of breast cancer cell apoptosis by novel thiouracil-fused heterocyclic compounds through boosting of Bax/Bcl-2 ratio and DFT study. Bioorg Chem. 2024;146:107292. doi: 10.1016/j.bioorg.2024.107292. PMID: 38555798.
  30. Mottaghi S, Abbaszadeh H. A comprehensive mechanistic insight into the dietary and estrogenic lignans, arctigenin and sesamin as potential anticarcinogenic and anticancer agents. Current status, challenges, and future perspectives. Crit Rev Food Sci and Nutr. 2022;62(26):7301-18. doi: 10.1080/10408398.2021.1913568. PMID: 33905270.
  31. Tannous S, Haykal T, Dhaini J, Hodroj MH, Rizk S. The anti-cancer effect of flaxseed lignan derivatives on different acute myeloid leukemia cancer cells. Biomed Pharmacother. 2020;132:110884. doi: 10.1016/j.biopha.2020.110884.PMID: 33080470.
Middle East Journal of Cancer
Volume 16, Issue 3
Summer 2025
Pages 258-266

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