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Year 2025, Volume: 10 Issue: 2, 124 - 134, 29.06.2025
https://doi.org/10.33457/ijhsrp.1643011

Abstract

Project Number

2022SABE015

References

  • N. Harbeck et al., Breast cancer, vol. 5, no. 1. 2019. doi: 10.1038/s41572-019-0111-2.
  • S. Loibl, P. Poortmans, M. Morrow, C. Denkert, and G. Curigliano, “Breast cancer,” The Lancet, vol. 397, no. 10286, pp. 1750–1769, 2021, doi: 10.1016/S0140-6736(20)32381-3.
  • N. Eliyatkin, E. Yalcin, B. Zengel, S. Aktaş, and E. Vardar, “Molecular Classification of Breast Carcinoma: From Traditional, Old-Fashioned Way to A New Age, and A New Way,” Journal of Breast Health, vol. 11, no. 2, pp. 59–66, 2015, doi: 10.5152/tjbh.2015.1669.
  • P. Eroles, A. Bosch, J. Alejandro Pérez-Fidalgo, and A. Lluch, “Molecular biology in breast cancer: Intrinsic subtypes and signaling pathways,” Cancer Treat Rev, vol. 38, no. 6, pp. 698–707, 2012, doi: 10.1016/j.ctrv.2011.11.005.
  • S. Dasari and P. Bernard Tchounwou, “Cisplatin in cancer therapy: Molecular mechanisms of action,” Eur J Pharmacol, vol. 740, pp. 364–378, 2014, doi: 10.1016/j.ejphar.2014.07.025.
  • T. Ozdemir-sanci and E. Alimogullari, “Effect of naringin and cisplatin combination on cell viability and cell death in bladder cancer cells,” Journal of Research in Pharmacy, vol. 29, no. 2, pp. 673–681, Apr. 2025, doi: 10.12991/JRESPHARM.1664894.
  • Y. Zhang et al., “The combinatory effects of natural products and chemotherapy drugs and their mechanisms in breast cancer treatment,” Phytochemistry Reviews, vol. 19, no. 5, pp. 1179–1197, 2020, doi: 10.1007/s11101-019-09628-w.
  • Y. T. Tang, Y. Li, P. Chu, X. D. Ma, Z. Y. Tang, and Z. L. Sun, “Molecular biological mechanism of action in cancer therapies: Juglone and its derivatives, the future of development,” Biomedicine and Pharmacotherapy, vol. 148, p. 112785, 2022, doi: 10.1016/j.biopha.2022.112785.
  • Y. Hu, Y. Shen, and Y. Li, “Effect of Pin1 inhibitor juglone on proliferation, migration and angiogenic ability of breast cancer cell line MCF7Adr,” Journal of Huazhong University of Science and Technology [Medical Sciences], vol. 35, no. 4, pp. 531–534, Aug. 2015, doi: 10.1007/s11596-015-1465-7.
  • Y. B. Ji, G. S. Xin, Z. Y. Qu, X. Zou, and M. Yu, “Mechanism of juglone-induced apoptosis of MCF-7 cells by the mitochondrial pathway,” Genetics and Molecular Research, vol. 15, no. 3, 2016, doi: 10.4238/gmr.15038785.
  • D. Erkoc-Kaya, H. Arikoglu, E. Guclu, D. Dursunoglu, and E. Menevse, “Juglone-ascorbate treatment enhances reactive oxygen species mediated mitochondrial apoptosis in pancreatic cancer,” Mol Biol Rep, vol. 51, no. 1, Dec. 2024, doi: 10.1007/S11033-024-09254-6.
  • E. Altan et al., “Fabrication of Electrospun Juglans regia (Juglone) Loaded Poly(lactic acid) Scaffolds as a Potential Wound Dressing Material,” Polymers (Basel), vol. 14, no. 10, May 2022, doi: 10.3390/POLYM14101971.
  • S. Hombach and M. Kretz, “Non-coding RNAs: Classification, biology and functioning,” Adv Exp Med Biol, vol. 937, pp. 3–17, 2016, doi: 10.1007/978-3-319-42059-2_1.
  • T. Ye, X. Yang, H. Liu, P. Lv, and Z. Ye, “Long non-coding RNA BLACAT1 in human cancers,” Onco Targets Ther, vol. 13, pp. 8263–8272, 2020, doi: 10.2147/OTT.S261461.
  • W. Kong et al., “MicroRNA-155 Is Regulated by the Transforming Growth Factor β/Smad Pathway and Contributes to Epithelial Cell Plasticity by Targeting RhoA,” Mol Cell Biol, vol. 28, no. 22, pp. 6773–6784, Nov. 2008, doi: 10.1128/MCB.00941-08.
  • B. Pasculli et al., “Hsa-miR-155-5p Up-Regulation in Breast Cancer and Its Relevance for Treatment With Poly[ADP-Ribose] Polymerase 1 (PARP-1) Inhibitors,” Front Oncol, vol. 10, no. August, pp. 1–14, 2020, doi: 10.3389/fonc.2020.01415.
  • Q. Hao, J. V. Vadgama, and P. Wang, “CCL2/CCR2 signaling in cancer pathogenesis,” Cell Communication and Signaling, vol. 18, no. 1, pp. 1–13, 2020, doi: 10.1186/s12964-020-00589-8.
  • M. Xu, Y. Wang, R. Xia, Y. Wei, and X. Wei, “Role of the CCL2-CCR2 signalling axis in cancer: Mechanisms and therapeutic targeting,” Cell Prolif, vol. 54, no. 10, pp. 1–17, 2021, doi: 10.1111/cpr.13115.
  • C. Zou et al., “Juglone Inhibits Tumor Metastasis by Regulating Stemness Characteristics and the Epithelial-to-Mesenchymal Transition in Cancer Cells both in Vitro and in Vivo,” Front Biosci (Landmark Ed), vol. 28, no. 2, p. 26, 2023, doi: 10.31083/j.fbl2802026.
  • X. Hu, Y. Liu, Y. Du, T. Cheng, and W. Xia, “Long non-coding RNA BLACAT1 promotes breast cancer cell proliferation and metastasis by miR-150-5p/CCR2,” Cell Biosci, vol. 9, no. 1, pp. 1–9, 2019, doi: 10.1186/s13578-019-0274-2.
  • J. Hu et al., “The CCR2 3’UTR functions as a competing endogenous RNA to inhibit breast cancer metastasis,” J Cell Sci, vol. 130, no. 19, pp. 3399–3413, 2017, doi: 10.1242/jcs.202127.
  • X. Liu, Y. Li, Z. Li, and T. Hou, “miR 155 promotes proliferation and epithelial mesenchymal transition of MCF 7 cells,” Exp Ther Med, vol. 21, no. 3, pp. 1–7, 2021, doi: 10.3892/etm.2021.9650.
  • B. Uslu, M. Yaman, T. Özdemir Sanci, M. Güngörmüş, Ç. Z. Köprü, and F. E. Güneş, “Acetone extracts of Berberis vulgaris and Cornus mas L. induce apoptosis in MCF-7 breast cancer cells,” Turk J Med Sci, vol. 53, no. 5, pp. 1476–1488, Oct. 2023, doi: 10.55730/1300-0144.5715.

INVESTIGATION OF THE EFFECTS OF JUGLONE AND CISPLATIN ON BREAST CANCER CELL LINES

Year 2025, Volume: 10 Issue: 2, 124 - 134, 29.06.2025
https://doi.org/10.33457/ijhsrp.1643011

Abstract

Breast cancer is one of the most commonly diagnosed malignancies worldwide, accounting for approximately 11% of all cancer-related deaths. Cisplatin induces DNA damage, thereby leading to apoptotic cell death, while juglone, a phytochemical compound, exhibits antioxidant and antiproliferative properties. BLACAT1, miR-155-5p, and CCR2 are non-coding RNAs implicated in breast cancer metastasis. This study aimed to investigate the effects of juglone and cisplatin on breast cancer cells by evaluating their impact on cell viability, gene expression, and invasive potential. MDA-MB-231 and MCF-7 breast cancer cell lines were treated with juglone and cisplatin. Cytotoxic effects were determined using the CCK-8 assay, while qPCR was employed to analyze changes in the expression levels of BLACAT1, miR-155-5p, and CCR2. The impact on cell invasion was assessed using the Transwell invasion assay. Juglone and cisplatin exhibited dose-dependent cytotoxicity in both cell lines. qPCR analysis revealed significant alterations in the expression levels of BLACAT1, miR-155-5p, and CCR2 following treatment. The Transwell invasion assay demonstrated that juglone and cisplatin affected the invasive potential of breast cancer cells, with notable differences observed between individual and combined treatments. Juglone and cisplatin modulate breast cancer cell viability, gene expression, and invasive behavior, with juglone demonstrating potential as a therapeutic agent, particularly for luminal-type breast cancer. However, the combined application did not enhance the therapeutic effect, suggesting a complex interaction between these agents.

Ethical Statement

This study does not require ethical approval.

Supporting Institution

Pamukkale University Scientific Research Projects Coordination Unit

Project Number

2022SABE015

Thanks

We would like to thank Pamukkale University Scientific Research Projects Coordination Unit for funding this study.

References

  • N. Harbeck et al., Breast cancer, vol. 5, no. 1. 2019. doi: 10.1038/s41572-019-0111-2.
  • S. Loibl, P. Poortmans, M. Morrow, C. Denkert, and G. Curigliano, “Breast cancer,” The Lancet, vol. 397, no. 10286, pp. 1750–1769, 2021, doi: 10.1016/S0140-6736(20)32381-3.
  • N. Eliyatkin, E. Yalcin, B. Zengel, S. Aktaş, and E. Vardar, “Molecular Classification of Breast Carcinoma: From Traditional, Old-Fashioned Way to A New Age, and A New Way,” Journal of Breast Health, vol. 11, no. 2, pp. 59–66, 2015, doi: 10.5152/tjbh.2015.1669.
  • P. Eroles, A. Bosch, J. Alejandro Pérez-Fidalgo, and A. Lluch, “Molecular biology in breast cancer: Intrinsic subtypes and signaling pathways,” Cancer Treat Rev, vol. 38, no. 6, pp. 698–707, 2012, doi: 10.1016/j.ctrv.2011.11.005.
  • S. Dasari and P. Bernard Tchounwou, “Cisplatin in cancer therapy: Molecular mechanisms of action,” Eur J Pharmacol, vol. 740, pp. 364–378, 2014, doi: 10.1016/j.ejphar.2014.07.025.
  • T. Ozdemir-sanci and E. Alimogullari, “Effect of naringin and cisplatin combination on cell viability and cell death in bladder cancer cells,” Journal of Research in Pharmacy, vol. 29, no. 2, pp. 673–681, Apr. 2025, doi: 10.12991/JRESPHARM.1664894.
  • Y. Zhang et al., “The combinatory effects of natural products and chemotherapy drugs and their mechanisms in breast cancer treatment,” Phytochemistry Reviews, vol. 19, no. 5, pp. 1179–1197, 2020, doi: 10.1007/s11101-019-09628-w.
  • Y. T. Tang, Y. Li, P. Chu, X. D. Ma, Z. Y. Tang, and Z. L. Sun, “Molecular biological mechanism of action in cancer therapies: Juglone and its derivatives, the future of development,” Biomedicine and Pharmacotherapy, vol. 148, p. 112785, 2022, doi: 10.1016/j.biopha.2022.112785.
  • Y. Hu, Y. Shen, and Y. Li, “Effect of Pin1 inhibitor juglone on proliferation, migration and angiogenic ability of breast cancer cell line MCF7Adr,” Journal of Huazhong University of Science and Technology [Medical Sciences], vol. 35, no. 4, pp. 531–534, Aug. 2015, doi: 10.1007/s11596-015-1465-7.
  • Y. B. Ji, G. S. Xin, Z. Y. Qu, X. Zou, and M. Yu, “Mechanism of juglone-induced apoptosis of MCF-7 cells by the mitochondrial pathway,” Genetics and Molecular Research, vol. 15, no. 3, 2016, doi: 10.4238/gmr.15038785.
  • D. Erkoc-Kaya, H. Arikoglu, E. Guclu, D. Dursunoglu, and E. Menevse, “Juglone-ascorbate treatment enhances reactive oxygen species mediated mitochondrial apoptosis in pancreatic cancer,” Mol Biol Rep, vol. 51, no. 1, Dec. 2024, doi: 10.1007/S11033-024-09254-6.
  • E. Altan et al., “Fabrication of Electrospun Juglans regia (Juglone) Loaded Poly(lactic acid) Scaffolds as a Potential Wound Dressing Material,” Polymers (Basel), vol. 14, no. 10, May 2022, doi: 10.3390/POLYM14101971.
  • S. Hombach and M. Kretz, “Non-coding RNAs: Classification, biology and functioning,” Adv Exp Med Biol, vol. 937, pp. 3–17, 2016, doi: 10.1007/978-3-319-42059-2_1.
  • T. Ye, X. Yang, H. Liu, P. Lv, and Z. Ye, “Long non-coding RNA BLACAT1 in human cancers,” Onco Targets Ther, vol. 13, pp. 8263–8272, 2020, doi: 10.2147/OTT.S261461.
  • W. Kong et al., “MicroRNA-155 Is Regulated by the Transforming Growth Factor β/Smad Pathway and Contributes to Epithelial Cell Plasticity by Targeting RhoA,” Mol Cell Biol, vol. 28, no. 22, pp. 6773–6784, Nov. 2008, doi: 10.1128/MCB.00941-08.
  • B. Pasculli et al., “Hsa-miR-155-5p Up-Regulation in Breast Cancer and Its Relevance for Treatment With Poly[ADP-Ribose] Polymerase 1 (PARP-1) Inhibitors,” Front Oncol, vol. 10, no. August, pp. 1–14, 2020, doi: 10.3389/fonc.2020.01415.
  • Q. Hao, J. V. Vadgama, and P. Wang, “CCL2/CCR2 signaling in cancer pathogenesis,” Cell Communication and Signaling, vol. 18, no. 1, pp. 1–13, 2020, doi: 10.1186/s12964-020-00589-8.
  • M. Xu, Y. Wang, R. Xia, Y. Wei, and X. Wei, “Role of the CCL2-CCR2 signalling axis in cancer: Mechanisms and therapeutic targeting,” Cell Prolif, vol. 54, no. 10, pp. 1–17, 2021, doi: 10.1111/cpr.13115.
  • C. Zou et al., “Juglone Inhibits Tumor Metastasis by Regulating Stemness Characteristics and the Epithelial-to-Mesenchymal Transition in Cancer Cells both in Vitro and in Vivo,” Front Biosci (Landmark Ed), vol. 28, no. 2, p. 26, 2023, doi: 10.31083/j.fbl2802026.
  • X. Hu, Y. Liu, Y. Du, T. Cheng, and W. Xia, “Long non-coding RNA BLACAT1 promotes breast cancer cell proliferation and metastasis by miR-150-5p/CCR2,” Cell Biosci, vol. 9, no. 1, pp. 1–9, 2019, doi: 10.1186/s13578-019-0274-2.
  • J. Hu et al., “The CCR2 3’UTR functions as a competing endogenous RNA to inhibit breast cancer metastasis,” J Cell Sci, vol. 130, no. 19, pp. 3399–3413, 2017, doi: 10.1242/jcs.202127.
  • X. Liu, Y. Li, Z. Li, and T. Hou, “miR 155 promotes proliferation and epithelial mesenchymal transition of MCF 7 cells,” Exp Ther Med, vol. 21, no. 3, pp. 1–7, 2021, doi: 10.3892/etm.2021.9650.
  • B. Uslu, M. Yaman, T. Özdemir Sanci, M. Güngörmüş, Ç. Z. Köprü, and F. E. Güneş, “Acetone extracts of Berberis vulgaris and Cornus mas L. induce apoptosis in MCF-7 breast cancer cells,” Turk J Med Sci, vol. 53, no. 5, pp. 1476–1488, Oct. 2023, doi: 10.55730/1300-0144.5715.
There are 23 citations in total.

Details

Primary Language English
Subjects Cancer Genetics, Cancer Cell Biology
Journal Section Article
Authors

Sacide Çakal 0009-0008-6851-5066

Buket Er Urgancı 0000-0002-5339-3835

Selda Şimşek 0000-0002-1585-7379

Project Number 2022SABE015
Publication Date June 29, 2025
Submission Date February 19, 2025
Acceptance Date June 3, 2025
Published in Issue Year 2025 Volume: 10 Issue: 2

Cite

IEEE S. Çakal, B. Er Urgancı, and S. Şimşek, “INVESTIGATION OF THE EFFECTS OF JUGLONE AND CISPLATIN ON BREAST CANCER CELL LINES”, IJHSRP, vol. 10, no. 2, pp. 124–134, 2025, doi: 10.33457/ijhsrp.1643011.

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