Research Article
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The cytotoxic and apoptotic effects of Thymus vulgaris extracts on human breast cancer cell lines

Year 2023, , 186 - 192, 30.08.2023
https://doi.org/10.26650/IstanbulJPharm.2023.1268463

Abstract

Background and Aims: Plant extracts are an important source of cytotoxic compounds and have consistently been an interesting field of research. The aim of this study is to investigate the cytotoxic and apoptotic effects of Thymus vulgaris (T. vulgaris) extracts on human breast cancer cell lines.
Methods: This study was carried out using human breast cancer cell lines (MCF-7 and MDA-MB-231) as experimental groups and the healthy human fibroblast cell line (PCS-201-012) as the control group. Petroleum ether and ethanol extracts were obtained from T. vulgaris. The extracts were applied to MCF-7 and MDA-MB-231 human breast cancer cell lines and human breast cancer stem cells. Cytotoxicity studies were performed using the RTCA iCELLigence system (Agilent Technologies), and apoptosis studies were performed using terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) and 4’,6-diamidino-2 phenylindole (DAPI) methods.
Results: The T. vulgaris extracts were found to have concentration-dependent cytotoxic effects on human breast cancer cells. The growth of breast cancer stem cells was also determined to be inhibited when an effective concentration (45 μg/ mL) of the extracts was applied. Lastly, specific morphological changes related to apoptosis were detected in the cells that had been treated with the effective concentration.
Conclusion: The T. vulgaris extracts were found to inhibit the proliferation of human breast cancer cells and human breast cancer stem cells selectively and concentration-dependently via an apoptosis-dependent pathway. The results suggest that the extracts may make promising sources for developing drugs for breast cancer therapy.

Supporting Institution

The Scientific Research Projects Coordination Unit of Istanbul University

Project Number

53695

Thanks

The present study was supported by The Scientific Research Projects Coordination Unit of Istanbul University (Project No. 53695).

References

  • Albeniz, G., & Alkanlı, N. (2020). Investigation of the relationship between methylenetetrahydrofolate reductase, methionine syn-thase reductase, methionine synthase gene variations and devel-opment of the Breast Cancer. In Alabaz. Ö (Ed), General Surgery (pp 19-37), İstanbul, TUR: Akademisyen Press. google scholar
  • Al-Hajj, M., Wicha, M. S., Benito-Hernandez, A., Morrison, S. J., & Clarke, M. F. (2003). Prospective identification of tumorigenic breast cancer cells. Proceedings of the National Academy of Scienc-es, 100(7), 3983-3988. https://doi.org/10.1073/pnas.0530291100 google scholar
  • Al-Shahrani, M. H., Mahfoud, M., Anvarbatcha, R., Athar, M. T., & Al Asmari, A. (2017). Evaluation of antifungal activity and cytotoxic-ity of Thymus vulgaris essential oil. Pharmacognosy Communica-tions, 7(1), 34-40. https://doi.org/10.5530/pc.2017.1.5 google scholar
  • Batlle, E., & Clevers, H. (2017). Cancer stem cells revisited. Nature Medicine, 23(10), 1124-1134. https://doi.org/10.1038/nm.4409 google scholar
  • Berdowska, I., Zielihski, B., Fecka, I., Kulbacka, J., Saczko, J., & Gam-ian, A. (2013). Cytotoxic impact of phenolics from Lamiaceae spe-cies on human breast cancer cells. Food Chemistry, 141(2), 13131321. https://doi.org/10.1016/j.foodchem.2013.03.090 google scholar
  • Berrington, D., & Lall, N. (2012). Anticancer activity of certain herbs and spices on the cervical epithelial carcinoma (HeLa) cell line. Evidence-Based Complementary and Alternative Medicine, 2012, Ar-ticle ID 564927. http://doi.org/10.1155/2012/564927 google scholar
  • Bone, K., & Mills, S. (2012). Principles and practice of phytotherapy: Modern Herbal Medicine. London, UK: Churchill Livingstone. google scholar
  • Bozorgi, A., Khazaei, M., & Khazaei, M. R. (2015). New findings on breast cancer stem cells: A review. Journal of Breast Cancer, 18(4), 303-312. http://doi.org/10.4048/jbc.2015.18.4.303 google scholar
  • Cragg, G. M., & Pezzuto, J. M. (2016). Natural products as a vital source for the discovery of cancer chemotherapeutic and che-mopreventive agents. Medical Principles and Practice, 25(Suppl. 2), 41-59. https://doi.org/10.1159/000443404 google scholar
  • Düzgün, Ş. A., Yerlikaya, A., Zeren, S., Bayhan, Z., Okur, E., & Boyacı, İ. (2017). Differential effects of p38 MAP kinase inhibitors SB203580 and SB202190 on growth and migration of human MDA-MB-231 cancer cell line. Cytotechnology, 69, 711-724. https://doi. org/10.1007/s10616-017-0079-2 google scholar
  • Esmaeili-Mahani, S., Falahi, F., & Yaghoobi, M. M. (2014). Pro-apoptotic and antiproliferative effects of Thymus caramanicus on human breast cancer cell line (MCF-7) and its interaction with anticancer drug vincristine. Evidence-Based Complemen-tary and Alternative Medicine, 2014, Article ID 893247. http://doi. org/10.1155/2014/893247 google scholar
  • Hanahan, D., & Weinberg, R. A. (2000). The hallmarks of cancer. Cell, 100(1), 57-70. https://doi.org/10.1016/S0092-8674(00)81683-9 google scholar
  • Hosseinzadeh, S., Jafarikukhdan, A., Hosseini, A., & Armand, R. (2015). The application of medicinal plants in traditional and modern medicine: A review of Thymus vulgaris. International Jour-nal of Clinical Medicine, 6(09), 635-642. https://doi.org/10.4236/ ijcm.2015.69084 google scholar
  • Kuete, V. (Ed.). (2017). Medicinal spices and vegetables from Af-rica: Therapeutic potential against metabolic, inflammatory, in-fectious and systemic diseases. Cambridge, MA: Academic Press. google scholar
  • Moe, B., Gabos, S., & Li, X. F. (2013). Real-time cell-microelectronic sensing of nanoparticle-induced cytotoxic effects. Analytica Chi-mica Acta, 789, 83-90. https://doi.org/10.1016/j.aca.2013.06.002 google scholar
  • Nikolic, M., Glamoclija, J., Ferreira, I. C., Calhelha, R. C., Fernandes, Â., Markovic, T., ... & Sokovic, M. (2014). Chemical composition, an-timicrobial, antioxidant and antitumor activity of Thymus serpyl-lum L., Thymus algeriensis Boiss. and Reut and Thymus vulgaris L. essential oils. Industrial Crops and Products, 52, 183-190. https:// doi.org/10.1016/j.indcrop.2013.10.006 google scholar
  • Roby, M. H. H., Sarhan, M. A., Selim, K. A. H., & Khalel, K. I. (2013). Evaluation of antioxidant activity, total phenols and phenolic compounds in thyme (Thymus vulgaris L.), sage (Salvia officina-lis L.), and marjoram (Origanum majorana L.) extracts. Industrial Crops and Products, 43, 827-831. https://doi.org/10.1016/j.ind-crop.2012.08.029 google scholar
  • Thomford, N. E., Senthebane, D. A., Rowe, A., Munro, D., Seele, P., Maroyi, A., & Dzobo, K. (2018). Natural products for drug discov-ery in the 21st century: Innovations for novel drug discovery. In-ternational Journal of Molecular Sciences, 19(6), 1578. https://doi. org/10.3390/ijms19061578 google scholar
  • Türker Şener, L., Albeniz, G., Dinc, B., & Albeniz, I. (2017). iCELLi-gence realtime cell analysis system for examining the cytotoxicity of drugs to cancer cell lines. Experimental and Therapeutic Medi-cine, 14(3), 1866-1870. https://doi.org/10.3892/etm.2017.4781 google scholar
  • Wong, R. S. (2011). Apoptosis in cancer: From pathogenesis to treatment. Journal of Experimental & Clinical Cancer Research, 30(1), 1-14. https://doi.org/10.1186/1756-9966-30-87 google scholar
  • Yin, Q. H., Yan, F. X., Zu, X. Y., Wu, Y. H., Wu, X. P., Liao, M. C., ... & Zhuang, Y. Z. (2012). Anti-proliferative and pro-apoptotic effect of carvacrol on human hepatocellular carcinoma cell line HepG-2. Cytotechnol-ogy, 64, 43-51. https://doi.org/10.1007/s10616-011-9389-y google scholar
  • Zheng, S., Xin, L., Liang, A., & Fu, Y. (2013). Cancer stem cell hy-pothesis: A brief summary and two proposals. Cytotechnology, 65, 505-512. https://doi.org/10.1007/s10616-012-9517-3 google scholar
Year 2023, , 186 - 192, 30.08.2023
https://doi.org/10.26650/IstanbulJPharm.2023.1268463

Abstract

Project Number

53695

References

  • Albeniz, G., & Alkanlı, N. (2020). Investigation of the relationship between methylenetetrahydrofolate reductase, methionine syn-thase reductase, methionine synthase gene variations and devel-opment of the Breast Cancer. In Alabaz. Ö (Ed), General Surgery (pp 19-37), İstanbul, TUR: Akademisyen Press. google scholar
  • Al-Hajj, M., Wicha, M. S., Benito-Hernandez, A., Morrison, S. J., & Clarke, M. F. (2003). Prospective identification of tumorigenic breast cancer cells. Proceedings of the National Academy of Scienc-es, 100(7), 3983-3988. https://doi.org/10.1073/pnas.0530291100 google scholar
  • Al-Shahrani, M. H., Mahfoud, M., Anvarbatcha, R., Athar, M. T., & Al Asmari, A. (2017). Evaluation of antifungal activity and cytotoxic-ity of Thymus vulgaris essential oil. Pharmacognosy Communica-tions, 7(1), 34-40. https://doi.org/10.5530/pc.2017.1.5 google scholar
  • Batlle, E., & Clevers, H. (2017). Cancer stem cells revisited. Nature Medicine, 23(10), 1124-1134. https://doi.org/10.1038/nm.4409 google scholar
  • Berdowska, I., Zielihski, B., Fecka, I., Kulbacka, J., Saczko, J., & Gam-ian, A. (2013). Cytotoxic impact of phenolics from Lamiaceae spe-cies on human breast cancer cells. Food Chemistry, 141(2), 13131321. https://doi.org/10.1016/j.foodchem.2013.03.090 google scholar
  • Berrington, D., & Lall, N. (2012). Anticancer activity of certain herbs and spices on the cervical epithelial carcinoma (HeLa) cell line. Evidence-Based Complementary and Alternative Medicine, 2012, Ar-ticle ID 564927. http://doi.org/10.1155/2012/564927 google scholar
  • Bone, K., & Mills, S. (2012). Principles and practice of phytotherapy: Modern Herbal Medicine. London, UK: Churchill Livingstone. google scholar
  • Bozorgi, A., Khazaei, M., & Khazaei, M. R. (2015). New findings on breast cancer stem cells: A review. Journal of Breast Cancer, 18(4), 303-312. http://doi.org/10.4048/jbc.2015.18.4.303 google scholar
  • Cragg, G. M., & Pezzuto, J. M. (2016). Natural products as a vital source for the discovery of cancer chemotherapeutic and che-mopreventive agents. Medical Principles and Practice, 25(Suppl. 2), 41-59. https://doi.org/10.1159/000443404 google scholar
  • Düzgün, Ş. A., Yerlikaya, A., Zeren, S., Bayhan, Z., Okur, E., & Boyacı, İ. (2017). Differential effects of p38 MAP kinase inhibitors SB203580 and SB202190 on growth and migration of human MDA-MB-231 cancer cell line. Cytotechnology, 69, 711-724. https://doi. org/10.1007/s10616-017-0079-2 google scholar
  • Esmaeili-Mahani, S., Falahi, F., & Yaghoobi, M. M. (2014). Pro-apoptotic and antiproliferative effects of Thymus caramanicus on human breast cancer cell line (MCF-7) and its interaction with anticancer drug vincristine. Evidence-Based Complemen-tary and Alternative Medicine, 2014, Article ID 893247. http://doi. org/10.1155/2014/893247 google scholar
  • Hanahan, D., & Weinberg, R. A. (2000). The hallmarks of cancer. Cell, 100(1), 57-70. https://doi.org/10.1016/S0092-8674(00)81683-9 google scholar
  • Hosseinzadeh, S., Jafarikukhdan, A., Hosseini, A., & Armand, R. (2015). The application of medicinal plants in traditional and modern medicine: A review of Thymus vulgaris. International Jour-nal of Clinical Medicine, 6(09), 635-642. https://doi.org/10.4236/ ijcm.2015.69084 google scholar
  • Kuete, V. (Ed.). (2017). Medicinal spices and vegetables from Af-rica: Therapeutic potential against metabolic, inflammatory, in-fectious and systemic diseases. Cambridge, MA: Academic Press. google scholar
  • Moe, B., Gabos, S., & Li, X. F. (2013). Real-time cell-microelectronic sensing of nanoparticle-induced cytotoxic effects. Analytica Chi-mica Acta, 789, 83-90. https://doi.org/10.1016/j.aca.2013.06.002 google scholar
  • Nikolic, M., Glamoclija, J., Ferreira, I. C., Calhelha, R. C., Fernandes, Â., Markovic, T., ... & Sokovic, M. (2014). Chemical composition, an-timicrobial, antioxidant and antitumor activity of Thymus serpyl-lum L., Thymus algeriensis Boiss. and Reut and Thymus vulgaris L. essential oils. Industrial Crops and Products, 52, 183-190. https:// doi.org/10.1016/j.indcrop.2013.10.006 google scholar
  • Roby, M. H. H., Sarhan, M. A., Selim, K. A. H., & Khalel, K. I. (2013). Evaluation of antioxidant activity, total phenols and phenolic compounds in thyme (Thymus vulgaris L.), sage (Salvia officina-lis L.), and marjoram (Origanum majorana L.) extracts. Industrial Crops and Products, 43, 827-831. https://doi.org/10.1016/j.ind-crop.2012.08.029 google scholar
  • Thomford, N. E., Senthebane, D. A., Rowe, A., Munro, D., Seele, P., Maroyi, A., & Dzobo, K. (2018). Natural products for drug discov-ery in the 21st century: Innovations for novel drug discovery. In-ternational Journal of Molecular Sciences, 19(6), 1578. https://doi. org/10.3390/ijms19061578 google scholar
  • Türker Şener, L., Albeniz, G., Dinc, B., & Albeniz, I. (2017). iCELLi-gence realtime cell analysis system for examining the cytotoxicity of drugs to cancer cell lines. Experimental and Therapeutic Medi-cine, 14(3), 1866-1870. https://doi.org/10.3892/etm.2017.4781 google scholar
  • Wong, R. S. (2011). Apoptosis in cancer: From pathogenesis to treatment. Journal of Experimental & Clinical Cancer Research, 30(1), 1-14. https://doi.org/10.1186/1756-9966-30-87 google scholar
  • Yin, Q. H., Yan, F. X., Zu, X. Y., Wu, Y. H., Wu, X. P., Liao, M. C., ... & Zhuang, Y. Z. (2012). Anti-proliferative and pro-apoptotic effect of carvacrol on human hepatocellular carcinoma cell line HepG-2. Cytotechnol-ogy, 64, 43-51. https://doi.org/10.1007/s10616-011-9389-y google scholar
  • Zheng, S., Xin, L., Liang, A., & Fu, Y. (2013). Cancer stem cell hy-pothesis: A brief summary and two proposals. Cytotechnology, 65, 505-512. https://doi.org/10.1007/s10616-012-9517-3 google scholar
There are 22 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Original Article
Authors

Yasin Çelikok 0000-0002-5633-4435

Leyla Turker Sener 0000-0002-7317-9086

Burcu Bütün 0000-0002-0797-7274

Işıl Albeniz 0000-0002-6005-5164

Project Number 53695
Publication Date August 30, 2023
Submission Date March 21, 2023
Published in Issue Year 2023

Cite

APA Çelikok, Y., Turker Sener, L., Bütün, B., Albeniz, I. (2023). The cytotoxic and apoptotic effects of Thymus vulgaris extracts on human breast cancer cell lines. İstanbul Journal of Pharmacy, 53(2), 186-192. https://doi.org/10.26650/IstanbulJPharm.2023.1268463
AMA Çelikok Y, Turker Sener L, Bütün B, Albeniz I. The cytotoxic and apoptotic effects of Thymus vulgaris extracts on human breast cancer cell lines. iujp. August 2023;53(2):186-192. doi:10.26650/IstanbulJPharm.2023.1268463
Chicago Çelikok, Yasin, Leyla Turker Sener, Burcu Bütün, and Işıl Albeniz. “The Cytotoxic and Apoptotic Effects of Thymus Vulgaris Extracts on Human Breast Cancer Cell Lines”. İstanbul Journal of Pharmacy 53, no. 2 (August 2023): 186-92. https://doi.org/10.26650/IstanbulJPharm.2023.1268463.
EndNote Çelikok Y, Turker Sener L, Bütün B, Albeniz I (August 1, 2023) The cytotoxic and apoptotic effects of Thymus vulgaris extracts on human breast cancer cell lines. İstanbul Journal of Pharmacy 53 2 186–192.
IEEE Y. Çelikok, L. Turker Sener, B. Bütün, and I. Albeniz, “The cytotoxic and apoptotic effects of Thymus vulgaris extracts on human breast cancer cell lines”, iujp, vol. 53, no. 2, pp. 186–192, 2023, doi: 10.26650/IstanbulJPharm.2023.1268463.
ISNAD Çelikok, Yasin et al. “The Cytotoxic and Apoptotic Effects of Thymus Vulgaris Extracts on Human Breast Cancer Cell Lines”. İstanbul Journal of Pharmacy 53/2 (August 2023), 186-192. https://doi.org/10.26650/IstanbulJPharm.2023.1268463.
JAMA Çelikok Y, Turker Sener L, Bütün B, Albeniz I. The cytotoxic and apoptotic effects of Thymus vulgaris extracts on human breast cancer cell lines. iujp. 2023;53:186–192.
MLA Çelikok, Yasin et al. “The Cytotoxic and Apoptotic Effects of Thymus Vulgaris Extracts on Human Breast Cancer Cell Lines”. İstanbul Journal of Pharmacy, vol. 53, no. 2, 2023, pp. 186-92, doi:10.26650/IstanbulJPharm.2023.1268463.
Vancouver Çelikok Y, Turker Sener L, Bütün B, Albeniz I. The cytotoxic and apoptotic effects of Thymus vulgaris extracts on human breast cancer cell lines. iujp. 2023;53(2):186-92.