Middle East Journal of Cancer

In Vitro Radiosensitization of T47D and MDA-MB-231 Breast Cancer Cells with the Neoflavonoid Dalbergin

Document Type : Original Article(s)

Authors

Fereshte Mahdizade Valojerdi 1
Bahram Goliaei 2
Nakisa Rezakhani 1
Alireza Nikoofar 3
Hoda Keshmiri Neghab 4
Mohammad Hasan Soheilifar 5
Bahareh Bigdeli 2

1 Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

2 Department of Biophysics, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran

3 Department of Radiotherapy, Iran University of Medical Sciences (IUMS), Tehran, Iran

4 Department of Photo Healing and Regeneration, Medical Laser Research Center, Yara Institute, ACECR, Tehran, Iran

5 Department of Medical Laser, Medical Laser Research Center, Yara Institute, ACECR, Tehran, Iran

https://doi.org/10.30476/mejc.2022.91913.1637
Abstract
Background: Radiotherapy is a frequently used therapeutic modality for breast cancer. Dalbergin, a natural antioxidant, inhibits carcinogens and tumor progression. In the present study, we investigated the effect of Dalbergin on the response of T47D and MDA-MB-231 breast cancer cell lines to ionizing radiation.
Method: In this experimental in vitro study, doubling time of T47D and MDAMB- 231 were obtained from the growth curve. The cytotoxic effect of Dalbergin on T47D and MDA-MB-231 breast cancer cells were estimated via MTT assay. To determine the clonogenic ability, we treated T47D and MDA-MB-231 with Dalbergin for 48 h prior to irradiation, subsequent to which a colony assay was performed. Real-time polymerase chain reaction was employed to determine the gene expression level.
Results: Dalbergin inhibited proliferation of T47D and MDA-MB-231 in a time and concentration-dependent manner. Additionally, the most appropriate time for the treatment of these types of cancer cells was found to be 48 h and the drug's concentration in both cell lines was different. The IC50 values of T47D and MDA-MB-231 cells were 0.001 and 0.0001 μM, respectively. Moreover, this drug radiaosensitizes both cell lines effectively compared with the radiation only. Finally, the gene expression level of p53, Bcl-2, and STAT3 were investigated in cancer cells.
Conclusion: Dalbergin showed apoptotic effects probably through the STAT/p53 signaling pathway. Therefore, Dalbergin could be considered as a radiosensitizer and its effects may be owing to increased cell death.

Keywords

Dalbergin
Cells
X-rays
Apoptotic
Cell death

How to cite this article:

Mahdizade Valojerdi F, Goliaei B, Rezakhani N, Nikoofar A, Keshmiri Neghab H, Soheilifar MH, et al. In vitro radiosensitization of T47D and MDA-MB-231 breast cancer cells with the Neoflavonoid Dalbergin. Middle East J Cancer. 2023;14(2):205-18. doi: 10.30476/mejc.2022 .91913.1637.

  1. Taghizadeh B, Ghavami L, Nikoofar A, Goliaei B. Equol as a potent radiosensitizer in estrogen receptorpositive and -negative human breast cancer cell lines. Breast Cancer. 2015;22(4):382-90. doi: 10.1007/s12282-013-0492-0.
  2. Kabała-Dzik A, Rzepecka-Stojko A, Kubina R, Jastrzębska-Stojko Ż, Stojko R, Wojtyczka RD, et al. Comparison of two components of propolis: Caffeic acid (CA) and caffeic acid phenethyl ester (CAPE) Induce apoptosis and cell cycle arrest of breast cancer cells MDA-MB-231. Molecules. 2017;22(9):1554. doi: 10.3390/molecules22091554.
  3. Bouquet F, Pal A, Pilones KA, Demaria S, Hann B, Akhurst RJ, et al. TGFβ1 inhibition increases the radiosensitivity of breast cancer cells in vitro and promotes tumor control by radiation in vivo. Clin Cancer Res. 2011;17(21):6754-65. doi: 10.1158/1078-0432.CCR-11-0544.
  4. Khoram NM, Bigdeli B, Nikoofar A, Goliaei B. Caffeic acid phenethyl ester increases radiosensitivity of estrogen receptor-positive and -negative breast cancer cells by prolonging radiation-induced DNA damage. J Breast Cancer. 2016;19(1):18-25. doi: 10.4048/jbc.2016.19.1.18.
  5. Filomeni G, Ciriolo MR. Redox control of apoptosis: an update. Antioxid Redox Signal. 2006;8(11-12):2187-92. doi: 10.1089/ars.2006.8.2187.
  6. Adewale AO, Adedeji SI, Olusola OO, Sulaiman SO, Victoria IO. Ethanolic extract of combined Cynodon dactylon and Mimosa pudica ameliorated experimentally induced benign prostatic hyperplasia in Wistar rats. J Infertil Reprod Biol. 2021;9(1):22-6. doi: 10.47277/JIRB/9(1)/22.
  7. Dehelean CA, Marcovici I, Soica C, Mioc M, Coricovac D, Iurciuc S, et al. Plant-derived anticancer compounds as new perspectives in drug discovery and alternative therapy. Molecules. 2021;26(4):1109. doi: 10.3390/molecules26041109.
  8. Trebaticka J, Ďuračkova Z. Psychiatric disorders and polyphenols: Can they be helpful in therapy? Oxid Med Cell Longev. 2015;2015:248529. doi: 10.1155/2015/248529.
  9. Tsao R. Chemistry and biochemistry of dietary polyphenols. Nutrients. 2010;2(12):1231-46. doi:10.3390/nu2121231.
  10. Al-Snafi AE. Chemical constituents and pharmacological effects of Dalbergia sissoo-A review. IOSR Journal of Pharmacy. 2017;7(2):59-71. doi:10.9790/3013-0702015971.
  11. Gao J, Zhang W, Ehrhardt A. Expanding the spectrum of adenoviral vectors for cancer therapy. Cancers (Basel). 2020;12(5):1139. doi: 10.3390/cancers12051139.
  12. Williams JR, Gridley DS, Slater JM. Radiobiology of radioresistant glioblastoma. In: Chen C, editor. Advances in the biology, imaging and therapies for glioblastoma. ISBN: 978-953-307-284-5, InTech 2011. Available from: http://www.intechopen.com/books/advances-in-the-biology-imaging-andtherapiesfor-glioblastoma/radiobiology-of-radioresistant-glioblastoma
  13. Yang YP, Chang YL, Huang PI, Chiou GY, Tseng LM, Chiou SH, et al. Resveratrol suppresses tumorigenicity and enhances radiosensitivity in primary glioblastoma tumor initiating cells by inhibiting the STAT3 axis. J Cell Physiol. 2012;227(3):976-93. doi: 10.1002/jcp.22806.
  14. Brammer I, Zoller M, Dikomey E. Relationship between cellular radiosensitivity and DNA damage measured by comet assay in human normal, NBS and AT fibroblasts. Int J Radiat Biol. 2001;77(9):929-38. doi: 10.1080/09553000110064222.
  15. Wada S, Kurahayashi H, Kobayashi Y, Funayama T, Yamamoto K, Natsuhori M, et al. The relationship between cellular radiosensitivity and radiation-induced DNA damage measured by the comet assay. J Vet Med Sci. 2003;65(4):471-7. doi: 10.1292/jvms.65.471.
  16. Kunkler IH, Canney P, van Tienhoven G, Russell NS; MRC/EORTC (BIG 2-04) SUPREMO Trial Management Group. Elucidating the role of chest wall irradiation in 'intermediate-risk' breast cancer: the MRC/EORTC SUPREMO trial. Clin Oncol (R Coll Radiol). 2008;20(1):31-4. doi: 10.1016/j.clon.2007.10.004.
  17. Eke I, Deuse Y, Hehlgans S, Gurtner K, Krause M, Baumann M, et al. β1Integrin/FAK/cortactin signaling is essential for human head and neck cancer resistance to radiotherapy. J Clin Invest. 2012;122(4):1529-40. doi: 10.1172/JCI61350.
  18. Gu HF, Mao XY, Du M. Prevention of breast cancer by dietary polyphenols-role of cancer stem cells. Crit Rev Food Sci Nutr. 2020;60(5):810-25. doi:10.1080/10408398.2018.1551778.
  19. Khoram NM, Bigdeli B, Nikoofar A, Goliaei B. Caffeic acid phenethyl ester increases radiosensitivity of estrogen receptor-positive and -negative breast cancer cells by prolonging radiation-induced DNA damage. J Breast Cancer. 2016;19(1):18-25. doi: 10.4048/jbc.2016.19.1.18.
  20. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003;100(7):3983-8. doi: 10.1073/pnas.0530291100.
  21. Kirkegaard T, Hansen SK, Larsen SL, Reiter BE, Sorensen BS, Lykkesfeldt AE. T47D breast cancer cells switch from ER/HER to HER/c-Src signaling upon acquiring resistance to the antiestrogen fulvestrant. Cancer Lett. 2014;344(1):90-100. doi:10.1016/j.canlet.2013.10.014.
  22. Chavez KJ, Garimella SV, Lipkowitz S. Triple negative breast cancer cell lines: one tool in the search for better treatment of triple negative breast cancer. Breast Dis. 2010;32(1-2):35-48. doi: 10.3233/BD-2010-0307.
  23. Anaya-Ruiz M, Bandala C, Perez-Santos JL. miR-485 acts as a tumor suppressor by inhibiting cell growth and migration in breast carcinoma T47D cells. Asian Pac J Cancer Prev. 2013;14(6):3757-60. doi:10.7314/apjcp.2013.14.6.3757.
  24. Adwan H, Bauerle TJ, Berger MR. Downregulation of osteopontin and bone sialoprotein II is related to reduced colony formation and metastasis formation of MDA-MB-231 human breast cancer cells. Cancer Gene Ther. 2004;11(2):109-20. doi: 10.1038/sj.cgt.7700659.
  25. Veuger SJ, Hunter JE, Durkacz BW. Ionizing radiationinduced NF-kappaB activation requires PARP-1 function to confer radioresistance. Oncogene. 2009;28(6):832-42. doi: 10.1038/onc.2008.439.
  26. Dubuc C, Savard M, Bovenzi V, Lessard A, Cote J, Neugebauer W, et al. Antitumor activity of cellpenetrant kinin B1 receptor antagonists in human triple-negative breast cancer cells. J Cell Physiol. 2019;234(3):2851-65. doi: 10.1002/jcp.27103.
  27. Patterson AV, Saunders MP, Greco O. Prodrugs in genetic chemoradiotherapy. Curr Pharm Des. 2003;9(26):2131-54. doi: 10.2174/1381612033454117.
  28. Zoberi I, Bradbury CM, Curry HA, Bisht KS, Goswami PC, Roti Roti JL, et al. Radiosensitizing and antiproliferative effects of resveratrol in two human cervical tumor cell lines. Cancer Lett. 2002;175(2):165-73. doi: 10.1016/s0304-3835(01)00719-4.
  29. Mu LH, Yan H, Wang YN, Yu TF, Liu P. Triterpenoid Saponins from Ardisia gigantifolia and mechanism on inhibiting proliferation of MDA-MB-231 cells. Biol Pharm Bull. 2019;42(2):194-200. doi: 10.1248/bpb.b18-00569.
  30. Deorukhkar A, Krishnan S. Targeting inflammatory pathways for tumor radiosensitization. Biochem Pharmacol. 2010;80(12):1904-14. doi: 10.1016/j.bcp.2010.06.039.
  31. Kabała-Dzik A, Rzepecka-Stojko A, Kubina R, Jastrzębska-Stojko Ż, Stojko R, Wojtyczka RD, et al. Comparison of two components of propolis: Caffeic acid (CA) and caffeic acid phenethyl ester (CAPE) induce apoptosis and cell cycle arrest of breast cancer cells MDA-MB-231. Molecules. 2017;22(9):1554. doi: 10.3390/molecules22091554.
  32. Dolara P, Luceri C, De Filippo C, Femia AP, Giovannelli L, Caderni G, et al. Red wine polyphenols influence carcinogenesis, intestinal microflora, oxidative damage and gene expression profiles of colonic mucosa in F344 rats. Mutat Res. 2005;591(1-2):237-46. doi: 10.1016/j.mrfmmm.2005.04.022.
  33. Lightbourn AV, Thomas RD. Crude edible fig (Ficus carica) leaf extract prevents diethylstilbestrol (DES)-induced DNA strand breaks in single-cell gel electrophoresis (SCGE)/comet assay: Literature review and pilot study. J Bioequivalence Bioavailab. 2019;11(2):19-28. doi: 10.35248/0975-0851.19.11.389.
  34. Ren B, Li D, Si L, Ding Y, Han J, Chen X, et al. Alteronol induces cell cycle arrest and apoptosis via increased reactive oxygen species production in human breast cancer T47D cells. J Pharm Pharmacol. 2018;70(4):516-24. doi: 10.1111/jphp.12879.
  35. Rezakhani N, Goliaei B, Parivar K, Nikoofar AR. Effects of X-irradiation and sinensetin on apoptosis induction in MDA-MB-231 human breast cancer cells. Int J Radiat Res. 2020;18(1):75-82. doi: 10.18869/acadpub.ijrr.18.1.75.

Home

Guide for Authors

Submit Manuscript

Guide for Reviewers

Contact Us