Investigation of the Effect of Conditioned Media of Mesenchymal Stem Cells Treated with Ascorbic Acid on Proliferative Behavior of Breast Cancer Cells

Subject Areas : Journal of Animal Biology

Fattane  Sam daliri ¹ (Department of Animal Sciences and Marine Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran)
Mahmood  Talkhabi ² (Department of Animal Sciences and Marine Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran)
Narges  Toolabi ³ (Department of Animal Sciences and Marine Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran)
Farnoosh  Attari ⁴ (Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran)
Mousa  Kehtari ⁵ (Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran)

Received: 2022-04-22 Accepted : 2022-06-14 Published : 2023-02-20

Keywords: breast cancer, Ascorbic acid, Cell Proliferation, Adipose-derived Mesenchymal Stem Cell, Conditioned Media,

Abstract :

Breast cancer is one of the most common types of cancer in women. Today, researchers are looking for new ways to treat cancer. One of the investigated approaches in the field of cancer is the use of stem cells. This study aimed to evaluate the proliferation and survival of 4T1 breast cancer cells in the presence of conditioned medium (CM) of mesenchymal stem cells treated with ascorbic acid (AA). Human adipose-derived mesenchymal stem cells (h-ADMSCs) and 4T1 breast cancer cells were used in this study. 4T1 cells were treated with different concentrations of AA and their viability was checked by MTT test. According to the results of previous studies and MTT test, 1 mM concentration was chosen to collect CM from h-ADMSCs. h-ADMSCs were divided into four groups: groups without FBS with and without AA (-FBS/± 1 mM AA) and groups containing 5% FBS with and without AA (5% FBS/± 1 mM AA). Then, the survival rate, colonization potential, cell cycle profile and apoptosis rate of 4T1 cells treated with different CMs were investigated. The results showed that CM in the -FBS/+AA group causes a decrease in the viability and proliferation of 4T1 cells compared to the -FBS/-AA group. Also, CM in the groups with FBS also showed similar results and the FBS/+AA group +5% decreased the survival and cell proliferation of 4T1 cells compared to the FBS/-AA+5% group. Also, CM caused changes in the cell cycle profile of 4T1 cells and their apoptosis rate in the studied groups. According to the results, it seems that ascorbic acid can decrease the survival and proliferation of 4T1 breast cancer cells by affecting the CM compounds obtained from h-ADMSCs.

References:

1. Akram M., Iqbal M., Daniyal M., Khan A.U. 2017. Awareness and current knowledge of breast cancer. Biological Research, 50(1):1-23.


2. Andrzejewska A., Lukomska B., Janowski M. 2019. Concise review: mesenchymal stem cells: from roots to boost. Stem Cells, 37(7):855-864.


3. Christodoulou I., Goulielmaki M., Devetzi M., Panagiotidis M, Koliakos G, Zoumpourlis V. 2018. Mesenchymal stem cells in preclinical cancer cytotherapy: a systematic review. Stem Cell Research and Therapy, 9(1):1-38.


4. Chu D.T., Nguyen T.T., Tien N.L., Tran D.K., Jeong J.H., Anh P.G., Dinh T.C. 2020. Recent progress of stem cell therapy in cancer treatment: molecular mechanisms and potential applications. Cells, 9(3):563.


5. D'Aniello C., Cermola F., Patriarca E.J., Minchiotti G. 2017. Vitamin C in stem cell biology: impact on extracellular matrix homeostasis and epigenetics. Stem Cells International, 2017:8936156.


6. Ding D.C., Shyu W.C., Lin S.Z. 2011. Mesenchymal stem cells. Cell Transplantation, 20(1):5-14.


7. Feng Y., Spezia M., Huang S., Yuan C., Zeng Z., Zhang L., Ren G. 2018. Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis. Genes and Diseases, 5(2):77-106.


8. Fernandes G., Barone A.W., Dziak R. 2017. The effect of ascorbic acid on bone cancer cells in vitro. Cogent Biology, 3(1):1288335.


9. Fernández-Lao C., Cantarero-Villanueva I., Fernández-de-las-Peñas C., Del-Moral-Ávila R., Menjón-Beltrán S., Arroyo-Morales M. Widespread mechanical pain hypersensitivity as a sign of central sensitization after breast cancer surgery: comparison between mastectomy and lumpectomy. Pain Medicine, 12(1):72-78.


10. Frömberg A., Gutsch D., Schulze D., Vollbracht C., Weiss G., Czubayko F., Aigner A. 2011. Ascorbate exerts anti-proliferative effects through cell cycle inhibition and sensitizes tumor cells towards cytostatic drugs. Cancer Chemotherapy and Pharmacology, 67(5):1157-1166.


11. Fu X., Liu G., Halim A., Ju Y., Luo Q., Song G. 2019. Mesenchymal stem cell migration and tissue repair. Cells, 8(8):784.


12. Fujisawa K., Hara K., Takami T., Okada S., Matsumoto T., Yamamoto N., Sakaida I. 2018. Evaluation of the effects of ascorbic acid on metabolism of human mesenchymal stem cells. Stem Cell Research and Therapy, 9(1):1-12.


13. Hmadcha A., Martin-Montalvo A., Gauthier B.R., Soria B., Capilla-Gonzalez V. 2020. Therapeutic potential of mesenchymal stem cells for cancer therapy. Frontiers in Bioengineering and Biotechnology, 8:43.


14. Ji X., Zhang Z., Han Y., Song J., Xu X., Jin J., Su S., Mu D., Liu X., Xu S., Cui H. 2016. Mesenchymal stem cells derived from normal gingival tissue inhibit the proliferation of oral cancer cells in vitro and in vivo. International Journal of Oncology, 49(5):2011-2022.


15. Kolak A., Kamińska M., Sygit K., Budny A., Surdyka D., Kukiełka-Budny B., Burdan F. 2017. Primary and secondary prevention of breast cancer. Annals of Agricultural and Environmental Medicine, 24(4): 549-553


16. Kolios G., Moodley Y. 2013. Introduction to stem cells and regenerative medicine. Respiration, 85(1):3-10.


17. Langroudi L., Hassan Z.M., Soleimani M., Hashemi S.M. 2015. Tumor associated mesenchymal stromal cells show higher immunosuppressive and angiogenic properties compared to adipose derived MSCs. Iranian Journal of Immunology, 12(4):226-239.


18. Lee Chong T., Ahearn E.L., Cimmino L. 2019. Reprogramming the epigenome with vitamin C. Frontiers in Cell and Developmental Biology, 7:128.


19. Lin W., Huang L., Li Y., Fang B., Li G., Chen L., Xu L. 2019. Mesenchymal stem cells and cancer: clinical challenges and opportunities. BioMed Research International, 2019: 2820853.


20. Ma Y., Chapman J., Levine M., Polireddy K.., Drisko J., Chen Q. 2014. High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy. Science Translational Medicine, 6(222):222ra18.


21. Mata A.M., Carvalho R.M., Alencar M.V., Cavalcante A.A., Silva B.B. 2016. Ascorbic acid in the prevention and treatment of cancer. Revista da Associação Médica Brasileira, 62:680-686.


22. Meleshina A.V., Cherkasova E.I., Shirmanova M.V., Klementieva N.V., Kiseleva E.V., Snopova L.В., Prodanets N.N., Zagaynova E.V. 2015. Influence of mesenchymal stem cells on metastasis development in mice in vivo. Stem Cell Research and Therapy, 6(1):1-10.


23. Naji A., Eitoku M., Favier B., Deschaseaux F., Rouas-Freiss N., Suganuma N. 2019. Biological functions of mesenchymal stem cells and clinical implications. Cellular and Molecular Life Sciences, 76(17):3323-3348.


24. Papaccio F., Paino F., Regad T., Papaccio G., Desiderio V., Tirino V. 2017. Concise review: cancer cells, cancer stem cells, and mesenchymal stem cells: influence in cancer development. Stem Cells Translational Medicine, 6(12):2115-2125


25. Pathi S.S., Lei P., Sreevalsan S., Chadalapaka G., Jutooru I., Safe S. 2011. Pharmacologic doses of ascorbic acid repress specificity protein (Sp) transcription factors and Sp-regulated genes in colon cancer cells. Nutrition and Cancer, 63(7):1133-1142.


26. Sun Y.S., Zhao Z., Yang Z.N., Xu F., Lu H.J., Zhu Z.Y., Shi W., Jiang J., Yao P.P., Zhu H.P. 2017. Risk factors and preventions of breast cancer. International Journal of Biological Sciences, 13(11):1387.


27. van der Valk J., Bieback K., Buta C., Cochrane B., Dirks W., Fu J., Hickman J., Hohensee C., Kolar R., Liebsch M., Pistollato F. 2018. Fetal bovine serum (FBS): past–present–future. Altex, 35(1):1-20.

Yang M., Teng S., Ma C., Yu Y., Wang P., Yi C. 2018. Ascorbic acid inhibits senescence in mesenchymal stem cells through ROS and AKT/mTOR signaling. Cytotechnology, 70(5): 1301-1313.