A Mini Review on Components of Flax Seed and Their Effects on Breast Cancer

Year 2024, Volume: 30 Issue: 2, 205 - 215, 26.03.2024

İrem Bayar , Senem Akkoç

https://doi.org/10.15832/ankutbd.1349777

Abstract

Breast cancer is recognized as one of the most common cancers worldwide that can lead to death. Alternative treatment options are needed due to drug resistance caused by current treatment methods such as chemotherapy, inclusion of healthy cells in the target, and possible side effects. In this context, there is great interest in natural compounds and their active metabolites. One of these is flaxseed (FS), which is one of the most studied foods to be associated with breast cancer. FS is a functional food with high nutritional value. FS components (fatty acids, fiber, and lignans) and especially the basic lignan structure in FS content, secoisolariciresinol diglucoside (SDG) and its metabolites enterolactone (ENL) and enterodiol (END) have beneficial effects on breast cancer progression. This review aimed to develop a perspective for further research on this type of cancer in the future by giving some general information about FS and its components and evaluating some studies showing potential effects on breast cancer.

Keywords

Chemotherapy, flaxseed, lignan, breast cancer, SDG.

References

• Almeida C F, Oliveira A, Ramos M J, Fernandes P A, Teixeira N & Amaral C (2020). Estrogen receptor-positive (ER+) breast cancer treatment: Are multi-target compounds the next promising approach? Biochemical Pharmacology 177: 113989
• Alphonse P A S & Aluko R E (2015). Anti-carcinogenic and anti-metastatic effects of flax seed lignan secolariciresinol diglucoside (SDG). Discovery Phytomedicine 2: 12-17
• Bak M J, Gupta S D, Wahler J & Suh N (2016). Role of dietary bioactive natural products in estrogen receptor-positive breast cancer. Seminars in Cancer Biology 40-41: 170-191
• Basu P & Maier C (2018). Phytoestrogens and breast cancer: In vitro anticancer activities of isoflavones, lignans, coumestans, stilbenes and their analogs and derivatives. Biomedicine&Pharmacoyherapy 107: 1648-1666
• Bernacchia R, Preti R & Vinci G (2014). Chemical Composition and Health Benefits of Flaxseed. Austin Journal of Nutrition and Food Sciences 2 (8):1045
• Bhimjiyani V H, Borugadda V B, Naik S & Dalai A K (2021). Enrichment of flaxseed ( Linum usitatissimum) oil with carotenoids of sea buckthorn pomace via ultrasound-assisted extraction technique: Enrichment of flaxseed oil with sea buckthorn. Current Research in Food Science 4: 478-488
• Bigdeli B, Goliaei B, Masoudi-Khoram N, Jooyan N, Nikoofar A, Rouhani M, Haghparast A & Mamashli F (2016). Enterolactone: A novel radiosensitizer for human breast cancer cell lines through impaired DNA repair and increased apoptosis. Toxicology and Applied Pharmacology 313: 18-194
• Bowers L W, Lineberger C G, Ford N A, Rossi E L, Punjala A, Camp K K, Kimler B K, Fabian C J & Hursting S D (2019). The flaxseed lignan secoisolariciresinol diglucoside decreases local inflammation, suppresses NFκB signaling, and inhibits mammary tumor growth. Breast Cancer Research and Treatment 173(3): 545-557
• Božović A, Mandušić V, Todorović L & Krajnović M (2021) Estrogen receptor beta: the promising biomarker and potential target in metastases. International Journal of Molecular Sciencies 22(4):1656
• Britt K L, Cuzick J & Philips K A (2020). Key steps for effective breast cancer prevention. Nature Reviews Cancer 20 (8): 417-436.
• Brooks J D & Thompson L U (2005). Mammalian lignans and genistein decrease the activities of aromatase and 17β-hydroxysteroid dehydrogenase in MCF-7 cells. The Journal of Steroid Biochemistry & Molecular Biology 94(5):461-467
• Buckner A L, Buckner C A, Montaut S & Lafrenie R M (2019). Treatment with flaxseed oil induces apoptosis in cultured malignant cells. Heliyon 9, 5(8): e02251
• Calado A, Neves P M, Santos T & Ravasco P (2018). The Effect of Flaxseed in Breast Cancer: A Literature Review. Frontiers in Nutrition 5: 4
• Cancer Today, Global Cancer Observatory. https://gco.iarc.fr/today/data/factsheets/populations/792-turkey-fact–sheets.pdf [accessed November 07, 2023]
• Ceccarelli I, Bioletti L, Peparini S, Solomita E, Ricci C, Casini I, Miceli E & Aloisi A M (2022). Estrogens and phytoestrogens in body functions. Nuroscience and Biobehavioral Reviews 132: 648-663
• Chang V C, Cotterchio M, Boucher B A, Jenkins D J A, Mirea L, McCann S E & Thompson L U (2019) Effect of Dietary Flaxseed Intake on Circulating Sex Hormone Levels among Postmenopausal Women: A Randomized Controlled Intervention Trial. Nutrition and Cancer 71(3): 385-398
• Chen J, Stavro P M & Thompson L U (2002). Dietary flaxseed inhibits human breast cancer growth and metastasis and downregulates expression of insulin-like growth factor and epidermal growth factor receptor. Nutrition and Cancer 43(2):187-192
• Chen J, Hui E, Ip T & Thompson L U (2004). Dietary flaxseed enhances the inhibitory effect of tamoxifen on the growth of estrogen-dependent human breast cancer (mcf-7) in nude mice. Clinical cancer research 10(22): 7703-7711
• Chen J, Wang L, Thompson L U (2006). Flaxseed and its components reduce metastasis after surgical excision of solid human breast tumor in nude mice. Cancer Letters 234(2): 168-175
• Chen J, Saggar J K, Corey P & Thompson L U (2009). Flaxseed and pure secoisolariciresinol diglucoside, but not flaxseed hull, reduce human breast tumor growth (MCF-7) in athymic mice. The Journal of Nutrition 139(11): 2061-2066
• Chhillar H, Chopra P & Ashfaq M A (2021). Lignans from linseed (Linum usitatissimum L.) and its allied species: Retrospect, introspect and prospect. Critical Reviews in Food Science and Nutrition 61(16): 2719-2741
• Daniel A R, Hagan C R & Lange C A (2011). Progesterone receptor action: defining a role in breast cancer. Expert Review of Endocrinology &Metabolism 6(3): 359-369
• da Luz F A C, Araújo B J & de Araújo R A (2022). The current staging and classification systems of breast cancer and their pitfalls: is it possible to integrate the complexity of this neoplasm into a unified staging system? Critical Reviews in Oncology/Hematology 178: 103781
• Das S, Kulkarni S, Singh Y, Kumar P & Thareja S (2022). Selective Estrogen Receptor Modulators (SERMs) for the treatment of ER+ breast cancer: An overview. Journal of Molecular Structure 1270: 133853
• Di Y, De Silva F, Krol E S & Alcorn J (2018). Flaxseed Lignans Enhance the Cytotoxicity of Chemotherapeutic Agents against Breast Cancer Cell Lines MDA-MB-231 and SKBR3. Nutrition and Cancer 70(2): 306-315
• Dobrowolska K & Regulska-Ilow B (2021). The legitimacy of using dietary supplement diglycoside secoisolariciresinol (SDG) from flaxseed in cancer. Roczniki Panstwowego Zakladu Higieny 72(1): 9-20
• Duffy C, Perez K & Partridge A (2007). Implications of phytoestrogen intake for breast cancer. CA: A Cancer Journal for Clinicians 57 (5): 260-277
• Feng Y, Spezia M, Huang S, Yuan C, Zeng Z, Zhang L, Ji X, Liu W, Huang B, Luo W, Liu B, Lei Y, Du S, Vuppalapati A, Luu H H, Haydon R C, He T C & Ren G (2018). Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis. Genes&Diseases 5(2): 77-106
• Fuentes N & Silveyra P (2019). Estrogen receptor signaling mechanisms. Advances in Protein Chemistry and Structural Biology 116: 135-170
• Global Cancer Observatory. http://gco.iarc.fr [accessed November 07, 2023]
• Gorzkiewicz J, Bartosz G & Sadowska-Bartosz I (2021). The Potential Effects of Phytoestrogens: The Role in Neuroprotection. Molecules 26(10): 2954
• Goyal A, Sharma V, Sihag M K, Tomar S K, Arora S, Sabikhi L & Singh A K (2015). Development and physico-chemical characterization of microencapsulated flaxseed oil powder: A functional ingredient for omega-3 fortification. Powder Technology 286: 527-537
• Goyal A, Sharma V, Upadhyay N, Gill S & Sihag M (2014). Flax and flaxseed oil: an ancient medicine & modern functional food. Journal of Food Science and Technology 51(9): 1633-1653
• Guerriero E, Sorice A, Capone F, Storti G, Colonna G, Ciliberto G & Costantini S (2017). Combining doxorubicin with a phenolic extract from flaxseed oil: Evaluation of the effect on two breast cancer cell lines. International Journal of Oncology 50(2): 468-476
• He Q, Hu H, Yang F, Song D, Zhang X & Dai X (2023). Advances in chimeric antigen receptor T cells therapy in the treatment of breast cancer. Biomedicine&Pharmacotherapy 162: 114609
• Helferich W G, Andrade J E & Hoagland M S (2008). Phytoestrogens and breast cancer: a complex story. Inflammopharmacology 16(5): 219-226
• Hilton H N, Clarke C L, Graham J D (2018). Estrogen and progesterone signalling in the normal breast and its implications for cancer development. Molecular and Cellular Endocrinology 466: 2-14
• Hu T, Linghu K, Huang S, Battino M, Georgiev M, Zengin G, Li D, Deng Y, Wang Y T & Cao H (2019). Flaxseed extract induces apoptosis in human breast cancer MCF-7 cells. Food and chemical toxicology 127:188-196
• Januškevičienė I & Petrikaité V (2019). Heterogeneity of breast cancer: the importance of interaction between different tumor cell populations. Life Science 239: 117009
• Kabel A M & Baali F H (2015). Breast Cancer: Insights into Risk Factors, Pathogenesis, Diagnosis and Management. Journal of Cancer Research and Treatment 3(2): 28-33
• Kajla P, Sharma A & Sood D R (2015). Flaxseed—a potential functional food source. Journal of Food Science and Technology 52(4): 1857-1871
• Kavousi M, Chavoshi M S (2020). Effect of coated carbon nanotubes with chitosan and cover of flaxseed in the induction of MDA-MB-231 apoptosis by analyzing the expression of Bax and Bcl-2. Meta Gene 26: 100807
• Khan G, Penttinen P, Cabanes A, Foxworth A, Chezek A, Mastropole K, Yu B, Smeds A, Halttunen T, Good C, Mӓkelӓ S & Hilakivi-Clarke L (2007). Maternal flaxseed diet during pregnancy or lactation increases female rat offspring's susceptibility to carcinogen-induced mammary tumorigenesis. Reproductive Toxicology 23(3): 397-406
• Khan M Z I, Uzair M, Nazli A & Chen J Z (2022). An overview on estrogen receptors signaling and its ligands in breast cancer. European Journal of Medicinal Chemistry 241: 114658
• Lee J & Cho K (2012). Flaxseed sprouts induce apoptosis and inhibit growth in MCF-7 and MDA-MB-231 human breast cancer cells. In Vitro Cellular&Developmental Biology Animal 48(4): 244-250
• Mal R, Magner A, David J, Datta J, Vallabhaneni M, Kassem M, Manouchehri J, Willingham N, Stover D, Vandeusen J, Sardesai S, Williams N, Wesolowski R, Lustberg M, Ganju R K, Ramaswamy B & Cherian M A (2020). Estrogen Receptor Beta (ERb): A Ligand Activated Tumor Suppressor. Frontiers in Oncology 10: 587386
• Mali A V, Wagh U V, Hegde M V, Chandorkar S S, Surve S V & Patole M V (2012). In vitro anti-metastatic activity of enterolactone, a mammalian lignan derived from flax lignan, and down-regulation of matrix metalloproteinases in MCF-7 and MDA MB 231 cell lines. Indian Journal of Cancer 49(1): 181-187
• Mansur A, Silva T C B F, Takada J Y, Avakian S D, Strunz C M C, César L A M, Aldrighi J M & Ramires J A F (2012). Long-term prospective study of the influence of estrone levels on events in postmenopausal women with or at high risk for coronary artery disease. The Scientific World Journal 2012: 363595
• Marghescu F I, Teodorescu M S & Radu D (2012). The Positive Impact of Flaxseed (Linum Usitatissimum) on Breast Cancer. Journal of Agroalimentary Processes and Technologies 18(2): 161-168
• Mason J K, Fu M, Chen J & Thompson L U (2015). Flaxseed oil enhances the effectiveness of trastuzumab in reducing the growth of HER2-overexpressing human breast tumors (BT-474). The Journal of Nutritional Biochemistry 26(1): 16-23
• Moar K, Pant A, Saini V, Pandey M, Maurya P K (2023). Potential diagnostic and prognostic biomarkers for breast cancer: A compiled review. Pathology-Research and Practice 251: 154893
• Moreira A C, Silva A M, Santos M S, Sardăo V A (2014). Phytoestrogens as alternative hormone replacement therapy in menopause: What is real, what is unknown. Journal of Steroid Biochemistry &Molecular Biology 143: 61-71
• Nazari E & Suja F (2016). Effects of 17β-estradiol (E2) on aqueous organisms and its treatment problem: a review. Reviews on Enviromental Health 31(4): 465-491
• Nikolić I L, Savić-Gajić I M, Tačić A D & Savić I M (2017). Classification and biological activity of phytoestrogens: a review. Advanced Technologies 6(2): 96-106
• Patel D, Vaghasiya J, Pancholi S S & Paul A (2012). Therapeutic Potential of Secoisolariciresinol Diglucoside: A Plant Lignan. International Journal of Pharmaceutical Sciences and Drug Research 4(1):15-18
• Paterni I, Granchi C, Katzenellenbogen J A & Minutolo F (2014). Estrogen receptors alpha (ERα) and beta (ERβ): Subtype-selective ligands and clinical potential. Steroids 90: 13-29
• Poschner S, Maier-Salamon A, Thalhammer T & Jӓger W (2019). Resveratrol and other dietary polyphenols are inhibitors of estrogen metabolism in human breast cancer cells. Journal of Steroid Biochemistry and Molecular Biology 190: 11-18
• Power K A & Thompson L U (2007). Can the combination of flaxseed and its lignans with soy and its isoflavones reduce the growth stimulatory effect of soy and its isoflavones on established breast cancer? Molecular Nutrition &Food Research 51(7): 845-856
• Power K A, Chen J M, Saarinen N M & Thompson L U (2008). Changes in biomarkers of estrogen receptor and growth factor signaling pathways in MCF-7 tumors after short- and long-term treatment with soy and flaxseed. Journal of Steroid Biochemistry & Molecular Biology 112(1-3):13-19
• Richter D U, Abarzua S, Chrobak M, Scholz C, Kuhn C, Schulze S, Kupka M S, Friese K, Briese V, Piechulla B & Jeschke U (2010). Effects of phytoestrogen extracts isolated from flax on estradiol production and ER/PR expression in MCF7 breast cancer cells. Anticancer research 30(5):1695-1699
• Rodríguez-García C, Sánchez-Quesada C, Toledo E, Delgado-Rodríguez M, Gaforio J J (2019). Naturally Lignan-Rich Foods: A Dietary Tool for Health Promotion? Molecules 24(5): 917
• Roy S S & Vadlamudi R K (2012). Role of Estrogen Receptor Signaling in Breast Cancer Metastasis. International Journal of Breast Cancer 2012: 654698
• Rubilar M, Gutiérrez C, Verdugo M, Shene C & Sineiro J (2010). Flaxseed as a source of functional ingredients. Journal of soil science and plant nutrition 10(3): 373-377
• Saarinen N M, Wӓrri A, Airio M, Smeds A & Mӓkelӓ S (2007). Role of dietary lignans in the reduction of breast cancer risk. Molecular Nutrition & Food Research 51(7): 857-866
• Saggar J K, Chen J, Corey P & Thompson L U (2015). Dietary flaxseed lignan or oil combined with tamoxifen treatment affects MCF-7 tumor growth through estrogen receptor- and growth factor-signaling pathways. Molecular Nutrition &Food Research 54 (3): 415-425.
• Samavat H & Kurzer M S (2015). Estrogen Metabolism and Breast Cancer. Cancer Letter 356(200): 231-243 Scherbakov A M, Stasevich O V, Salnikova D I, Andreeva O E & Mikhaevich E I (2021). Antiestrogenic and antiproliferative potency of secoisolariciresinol diglucoside derivatives on MCF-7 breast cancer cells. Natural Product Research 35(24): 6099-6105
• Schwartz N, Verma A, Bivens C B, Schwartz Z, Boyan B D (2016). Rapid steroid hormone actions via membrane receptors. Biochimica et Biophysica Acta 1863(9): 2289-2298
• Seibold P, Vrielling A, Johnson T S, Buck K, Behrens S, Kaaks R, Linseisen J, Obi N, Heinz J, Flesch-Janys D & Chang-Claude J (2014). Enterolactone concentrations and prognosis after postmenopausal breast cancer: Assessment of effect modification and meta-analysis. International Journal of Cancer 135(4): 923-933
• Sharma G N, Dave R, Sanadya J, Sharma P & Sharma K K (2010). Various types and management of breast cancer: an overview. Journal of Advanced Pharmaceutical Technology & Research 1 (2):109-126.
• Simopoulos A P (2002). The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomedicine and Pharmacotherapy 56(8): 365-379
• Smolarz B, Nowak A N & Romanowicz H (2022). Breast Cancer—Epidemiology, Classification, Pathogenesis and Treatment (Review of Literature). Cancers 14(10): 2569
• Taibi A, Lin Z, Tsao R, Thompson LU & Comelli E M (2019). Effects of Flaxseed and Its Components on Mammary Gland MiRNome: Identification of Potential Biomarkers to Prevent Breast Cancer Development. Nutrients 11(11): 2656 Tang Y, Wang Y, Kiani M F & Wang B (2016). Classification, Treatment Strategy, and Associated Drug Resistance in Breast Cancer. Clinical Breast Cancer 16(5): 335-343
• Tannous S, Haykal T, Dhaini J, Hodroj M H & Rizk S (2020). The anti-cancer effect of flaxseed lignan derivatives on different acute myeloid leukemia cancer cells. Biomedicine&Pharmacotherapie 132: 110884
• Tanwar A K, Dhiman N, Kumar A & Jaitak V (2021). Engagement of phytoestrogens in breast cancer suppression: Structural classification and mechanistic approach. European Journal of Medicinal Chemistry 213: 113037
• Torrens-Mas M & Roca P (2020). Phytoestrogens for Cancer Prevention and Treatment. Biology 9(12): 427 Touré A & Xueming X (2010). Flaxseed Lignans: Source, Biosynthesis, Metabolism, Antioxidant Activity, Bio-Active Components, and Health Benefits. Reviews in Food Science and Food Safety 9: 259-328
• Truan J S, Chen J M & Thompson L U (2010). Flaxseed oil reduces the growth of human breast tumors (MCF-7) at high levels of circulating estrogen. Molecular Nutrition & Food Research 54(10): 1414-1421
• Turner N C, Neven P, Loibl S & Andre F (2017). Advances in the treatment of advanced oestrogen-receptor-positive breast cancer. The Lancet 389(10087): 2403-2414
• Twelves C, Jove M, Gombos A & Awada A (2016). Cytotoxic chemotherapy: Still the mainstay of clinical practice for all subtypes metastatic breast cancer. Critical Reviews in Oncology/Hematology 100: 74-87
• Velentzis L S, Woodside J V, Cantwell M, Leathem A J & Keshtgar M R (2008). Do phytoestrogens reduce the risk of breast cancer and breast cancer recurrence? What clinicians need to know. European Journal of Cancer 44(13): 1799-1806
• Wang Z, Li Y, Ahmad A, Azmi A S, Banerjee S, Kong D & Sarkar F H (2010). Targeting Notch signaling pathway to overcome drug resistance for cancer therapy. Biochimica et Biophysica Acta 1806(2): 258-267
• Westcott N D & Muír A D (2003). Flax seed lignan in disease prevention and health promotion. Phytochemistry Reviews 2: 401-417
• Wiggins A K A, Mason J K, Thompson L U (2015). Growth and gene expression differ over time in alpha-linolenic acid treated breast cancer cells. Experimental Cell Research 333(1): 147-154
• Xiong X Y, Hu X J, Li Y, Liu C M (2015). Inhibitory Effects of Enterolactone on Growth and Metastasis in Human Breast Cancer. Nutrition and Cancer 67(8): 1326-1332
• Xing M, Wang J, Yang Q, Wang Y, Li J, Xiong J & Zhou S (2019). FKBP12 is a predictive biomarker for efficacy of anthracycline-based chemotherapy in breast cancer. Cancer Chemotherapy and Pharmacology 84: 861-872
• Yue W, Yager J D, Wang J P, Jupe E R & Santen R J (2013). Estrogen receptor-dependent and independent mechanisms of breast cancer carcinogenesis. Steroids 78(2): 161-170
• Zhang Q Y, Wang F X, Jia K K & Kong L D (2018). Natural Product Interventions for Chemotherapy and Radiotherapy-Induced Side Effects. Frontiers in Pharmacology 9: 1253
• Zhang W, Wang X, Liu Y, Tian H, Flickinger B, Empie M W & Sun S Z (2008). Effects of dietary flaxseed lignan extract on symptoms of benign prostatic hyperplasia. Journal of Medicinal Food 11(2): 207–214