Nutrition Research and Practice

The Korean Nutrition Society (한국영양학회)
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A combination of myokines and genistein suppresses cancer stemness in MCF-7 human breast cancer cells

  • Hyeji Kwon (Graduate Program in System Health Science and Engineering, Ewha Womans University) ;
  • Yuri Kim (Graduate Program in System Health Science and Engineering, Ewha Womans University) ;
  • Jung Hyun Kim (Department of Physical Education, Chung-Ang University)
  • Received : 2024.01.29
  • Accepted : 2024.05.02
  • Published : 2024.06.01
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Abstract

BACKGROUND/OBJECTIVES: Breast cancer is considered a serious health issue worldwide and is influenced by risk factors, including physical inactivity and unhealthy diet. Myokines secreted by muscles during physical activity play a crucial role in cancer development and the immune system. Genistein (Gen), an isoflavone primarily in legumes, induces anti-cancer activity by regulating cancer stem cells (CSCs). Therefore, this study investigated the potential anti-cancer effect of a combination of myokine and Gen on the human breast cancer MCF-7 cells. MATERIALS/METHODS: MCF-7, a human breast cancer cell line, was used for in vitro study. The cell viability of MCF-7 cells was evaluated in response to treatment with myokines, irisin (Iri), oncostatin M (OSM), and Gen using the MTT assay. Clonogenic and sphere formation assays were used to evaluate the self-renewal capacity of breast CSCs. The mRNA expression levels of stem cell markers were analyzed in MCF-7 breast cancer cells. RESULTS: Administering Iri or OSM with Gen significantly inhibited the self-renewal capacity of MCF-7 cells. In addition, mRNA expression of breast CSC markers SOX2 and OCT4, which are characteristic of CSCs, was suppressed by both myokine and Gen. However, combining Iri or OSM with Gen was the most effective treatment. CONCLUSION: These results suggested that combining Iri or OSM with Gen has an additive effect on breast CSCs by regulating self-renewal capacity and expression of CSCs markers. Therefore, the combination of myokines and Gen may have the therapeutic potential for treating breast cancer and improving the quality of life of cancer patients.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea Grant funded by the Korean government (MEST; NRF2022R1F1A1072466) and the BK21 FOUR (Fostering Outstanding Universities for Research) funded by the Ministry of Education (MOE, Korea) and National Research Foundation of Korea (NRF-5199990614253, Education Research Center for 4IR-Based Health Care).

References

  1. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin 2023;73:17-48.
  2. Heer E, Harper A, Escandor N, Sung H, McCormack V, Fidler-Benaoudia MM. Global burden and trends in premenopausal and postmenopausal breast cancer: a population-based study. Lancet Glob Health 2020;8:e1027-37.
  3. Jemal A, Center MM, DeSantis C, Ward EM. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev 2010;19:1893-907.
  4. Gopinath A, Cheema AH, Chaludiya K, Khalid M, Nwosu M, Agyeman WY, Bisht A, Venugopal S. The impact of dietary fat on breast cancer incidence and survival: a systematic review. Cureus 2022;14:e30003.
  5. Ayob AZ, Ramasamy TS. Cancer stem cells as key drivers of tumour progression. J Biomed Sci 2018;25:20.
  6. Aponte PM, Caicedo A. Stemness in cancer: stem cells, cancer stem cells, and their microenvironment. Stem Cells Int 2017;2017:5619472.
  7. Chang JC. Cancer stem cells: role in tumor growth, recurrence, metastasis, and treatment resistance. Medicine (Baltimore) 2016;95:S20-5.
  8. Friedenreich CM, Orenstein MR. Physical activity and cancer prevention: etiologic evidence and biological mechanisms. J Nutr 2002;132:3456S-3464S.
  9. Jiang Y, Wang W. Potential mechanisms of cancer prevention by weight control. Biophys Rev Lett 2008;3:421-37.
  10. Diaz BB, Gonzalez DA, Gannar F, Perez MCR, de Leon AC. Myokines, physical activity, insulin resistance and autoimmune diseases. Immunol Lett 2018;203:1-5.
  11. Hojman P. Exercise protects from cancer through regulation of immune function and inflammation. Biochem Soc Trans 2017;45:905-11.
  12. Hojman P, Dethlefsen C, Brandt C, Hansen J, Pedersen L, Pedersen BK. Exercise-induced muscle-derived cytokines inhibit mammary cancer cell growth. Am J Physiol Endocrinol Metab 2011;301:E504-10.
  13. Cebulski K, Nowinska K, Jablonska K, Romanowicz H, Smolarz B, Dziegiel P, Podhorska-Okolow M. Expression of irisin/FNDC5 in breast cancer. Int J Mol Sci 2022;23:23.
  14. Masjedi A, Hajizadeh F, Beigi Dargani F, Beyzai B, Aksoun M, Hojjat-Farsangi M, Zekiy A, Jadidi-Niaragh F, Oncostatin M. Oncostatin M: a mysterious cytokine in cancers. Int Immunopharmacol 2021;90:107158.
  15. Hutt JA, DeWille JW. Oncostatin M induces growth arrest of mammary epithelium via a CCAAT/enhancer-binding protein delta-dependent pathway. Mol Cancer Ther 2002;1:601-10. 
  16. Holzer RG, Ryan RE, Tommack M, Schlekeway E, Jorcyk CL. Oncostatin M stimulates the detachment of a reservoir of invasive mammary carcinoma cells: role of cyclooxygenase-2. Clin Exp Metastasis 2004;21:167-76.
  17. Haider T, Pandey V, Banjare N, Gupta PN, Soni V. Drug resistance in cancer: mechanisms and tackling strategies. Pharmacol Rep 2020;72:1125-51.
  18. Mukund V. Genistein: its role in breast cancer growth and metastasis. Curr Drug Metab 2020;21:6-10.
  19. Banerjee S, Li Y, Wang Z, Sarkar FH. Multi-targeted therapy of cancer by genistein. Cancer Lett 2008;269:226-42. 
  20. Sharifi-Rad J, Quispe C, Imran M, Rauf A, Nadeem M, Gondal TA, Ahmad B, Atif M, Mubarak MS, Sytar O, et al. Genistein: an integrative overview of its mode of action, pharmacological properties, and health benefits. Oxid Med Cell Longev 2021;2021:3268136.
  21. Goh YX, Jalil J, Lam KW, Husain K, Premakumar CM. Genistein: a review on its anti-inflammatory properties. Front Pharmacol 2022;13:820969.
  22. Sutrisno S, Aprina H, Simanungkalit HM, Andriyani A, Barlianto W, Sujuti H, Santoso S, Dwijayasa PM, Wahyuni ES, Mustofa E. Genistein modulates the estrogen receptor and suppresses angiogenesis and inflammation in the murine model of peritoneal endometriosis. J Tradit Complement Med 2017;8:278-81.
  23. Wang B, Xu H, Hu X, Ma W, Zhang J, Li Y, Yu M, Zhang Y, Li X, Ye X. Synergetic inhibition of daidzein and regular exercise on breast cancer in bearing-4T1 mice by regulating NK cells and apoptosis pathway. Life Sci 2020;245:117387.
  24. Franken NA, Rodermond HM, Stap J, Haveman J, van Bree C. Clonogenic assay of cells in vitro. Nat Protoc 2006;1:2315-9.
  25. Song S, Seo D. Cancer stem cells: biological features and targeted therapeutics. Hanyang Med Rev 2015;35:250.
  26. Fan P, Fan S, Wang H, Mao J, Shi Y, Ibrahim MM, Ma W, Yu X, Hou Z, Wang B, et al. Genistein decreases the breast cancer stem-like cell population through Hedgehog pathway. Stem Cell Res Ther 2013;4:146.
  27. Shao L, Li H, Chen J, Song H, Zhang Y, Wu F, Wang W, Zhang W, Wang F, Li H, et al. Irisin suppresses the migration, proliferation, and invasion of lung cancer cells via inhibition of epithelial-to-mesenchymal transition. Biochem Biophys Res Commun 2017;485:598-605.
  28. Yamashita T, Honda M, Nio K, Nakamoto Y, Yamashita T, Takamura H, Tani T, Zen Y, Kaneko S. Oncostatin m renders epithelial cell adhesion molecule-positive liver cancer stem cells sensitive to 5-fluorouracil by inducing hepatocytic differentiation. Cancer Res 2010;70:4687-97.
  29. Li C, Ahlborn TE, Kraemer FB, Liu J. Oncostatin M-induced growth inhibition and morphological changes of MDA-MB231 breast cancer cells are abolished by blocking the MEK/ERK signaling pathway. Breast Cancer Res Treat 2001;66:111-21.
  30. Ma W, Zhang Y, Yu M, Wang B, Xu S, Zhang J, Li X, Ye X. In-vitro and in-vivo anti-breast cancer activity of synergistic effect of berberine and exercise through promoting the apoptosis and immunomodulatory effects. Int Immunopharmacol 2020;87:106787.