Repurposing of Triazole Drugs to Combat Common Cancer Cases
Year 2023,
Volume: 11 Issue: 1, 276 - 287, 31.01.2023
Sevilay Cengiz
,
Berna Kavakcıoğlu Yardımcı
Abstract
Cancer with its prevalence and high mortality rates is an important problem that health authorities are trying to deal with all over the world. According to the data of the International Agency for Research on Cancer, 19.3 million new cancer cases occurred worldwide in 2020, and unfortunately, about 10 million of them resulted in death. The discovery of new drugs is compulsory due to restrictions such as the side effects of currently used anti-cancer drugs, drug resistance developing over time, and so on. Unfortunately the development of novel drugs requires especially a long time and a huge amount of cost. At this point, the repurposing approach, which refers to the secondary use of various drugs that was approved by FDA for other purposes, has a vital importance. In this study, the anti-proliferative effects of ICZ and FCZ, which are actually antifungal drugs, on breast (MCF-7 and MDA-MB-231) and lung (A549) cancer cells were evaluated. Results revealed that both of the drugs had a low inhibitory effect on A549 cell proliferation, whereas they caused promising inhibition on MCF-7 and MDA-MB-231 cell proliferation.
Thanks
ACKNOWLEDGEMENTS: The authors would like to thank Prof. Dr. Vural Küçükatay and his staff from Pamukkale University, Faculty of Medicine, and Department of Physiology, who opened their laboratory to them and offered all their equipment to their use.
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Triazol İlaçlarının Yaygın Kanser Vakalarıyla Mücadelede Yeniden Kullanımı
Year 2023,
Volume: 11 Issue: 1, 276 - 287, 31.01.2023
Sevilay Cengiz
,
Berna Kavakcıoğlu Yardımcı
Abstract
Yaygınlığı ve yüksek ölüm oranları ile kanser, tüm dünyada sağlık otoritelerinin başa çıkmaya çalıştığı önemli bir sorundur. Uluslararası Kanser Araştırmaları Ajansı'nın verilerine göre 2020 yılında dünya genelinde 19.3 milyon yeni kanser vakası meydana gelmiş ve ne yazık ki, bunların yaklaşık 10 milyonu ölümle sonuçlanmıştır. Halihazırda kullanılan anti-kanser ilaçlarının yan etkileri, zamanla gelişen ilaç direnci vb. kısıtlamalar nedeniyle yeni ilaçların keşfi zorunludur. Ne yazık ki, yeni ilaçların geliştirilmesi özellikle uzun bir zaman ve büyük bir maliyet gerektirmektedir. Bu noktada FDA tarafından farklı amaçlarla onaylanan çeşitli ilaçların başka amaçlarla sekonder kullanımını ifade eden yeniden kullanım yaklaşımı hayati bir önem taşımaktadır. Bu çalışmada aslında antifungal ilaçlar olan ICZ ve FCZ'nin meme (MCF-7 ve MDA-MB-231) ve akciğer (A549) kanser hücreleri üzerindeki antiproliferatif etkileri değerlendirilmiştir. Sonuçlar, her iki ilacın da A549 hücre proliferasyonu üzerinde düşük bir inhibitör etkiye sahip olduğunu, buna karşın MCF-7 ve MDA-MB-231 hücre proliferasyonu üzerinde umut verici bir inhibisyona neden olduklarını ortaya koymuştur.
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- [6] A. Correia, D. Silva, A. Correia, M. Vilanova, F. Gärtner and N. Vale, “Study of New Therapeutic Strategies to Combat Breast Cancer Using Drug Combinations,” Biomolecules, vol. 8(4), Dec. 2018, Art no.175, doi:10.3390/biom8040175.
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- [10] S. Aminzadeh-Gohari, D.D. Weber, S. Vidali, L. Catalano, B. Kofler and R.G. Feichtinger, “From old to new - repurposing drugs to target mitochondrial energy metabolism in cancer,” Semin Cell Dev Biol, vol. 98, pp. 211-223, Feb. 2020, doi:10.1016/j.semcdb.2019.05.025.
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- [14] J.J. Hernandez, M. Pryszlak, L. Smith, C. Yanchus, N. Kurji, V.M. Shahani and S.V. Molinski, "Giving Drugs a Second Chance: Overcoming Regulatory and Financial Hurdles in Repurposing Approved Drugs as Cancer Therapeutics,” Front Oncol, vol. 7, Nov. 2017, Art no. 273, doi:10.3389/fonc.2017.00273.
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- [18] M.D. Radmacher and R. Simon, “Estimation of tamoxifen's efficacy for preventing the formation and growth of breast tumors,” J Natl Cancer Inst, vol. 92(1), pp. 48-53, Jan 2000, doi:10.1093/jnci/92.1.48.
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- [21] S.H. Bae, J.H. Park, H.G. Choi, H. Kim and S.H. Kim, “Imidazole Antifungal Drugs Inhibit the Cell Proliferation and Invasion of Human Breast Cancer Cells,” Biomol Ther, vol. 26(5), pp. 494-502, Sep 2018, doi:10.4062/biomolther.2018.042.
- [22] N. Somchit, S.M. Hassim and S.H. Samsudin, “Itraconazole and fuconazole-induced toxicity in rat hepatocytes: a comparative in vitro study,” Hum Exp Toxicol, vol. 21(1), pp. 43-48, Jan 2002, doi:10.1191/0960327102ht208oa.
- [23] N. Somchit, A.R. Norshahida, A.H. Hasiah, A. Zuraini, M.R. Sulaiman and M.M. Noordin, “Hepatotoxicity induced by antifungal drugs itraconazole and fuconazole in rats: a comparative in vivo study,” Hum Exp Toxicol, vol. 23(11), pp. 519-525, Nov 2004, doi:10.1191/0960327104ht479oa.
- [24] X. Wang, S. Wei, Y. Zhao, C. Shi, P. Liu, C. Zhang, Y. Lei, B. Zhang, B. Bai, Y. Huang and H. Zhang, “Anti-proliferation of breast cancer cells with itraconazole: Hedgehog pathway inhibition induces apoptosis and autophagic cell death,” Cancer Lett, vol. 385, pp. 128-136, Jan 2017, doi:10.1016/j.canlet.2016.10.034.
- [25] R.M. dos Santos Correa, T.C. Mota, A.C. Guimarães, L.T. Bonfim, R.R. Burbano and M. de Oliveira Bahia, “Cytotoxic and Genotoxic Effects of Fluconazole on African Green Monkey Kidney (Vero) Cell Line,” Biomed Res Int, Nov 2018, Art no. 6271547, doi:10.1155/2018/6271547.
- [26] R.J. Rodriguez and D. Jr. Acosta, “Comparison of ketoconazole- and fluconazole-induced hepatotoxicity in a primary culture system of rat hepatocytes,” Toxicology, vol. 96(2), pp. 83-92, Feb 1995, doi:10.1016/0300-483x(94)02911-d.
- [27] De Logu, M. Saddi, M.C. Cardia, R. Borgna, C. Sanna, B. Saddi and E. Maccioni, “In vitro activity of 2-cyclohexylidenhydrazo-4-phenyl-thiazole compared with those of amphotericin B and fluconazole against clinical isolates of Candida spp. and fluconazole-resistant Candida albicans,” J Antimicrob Chemother, vol. 55(5), pp. 692-698, May 2005, doi:10.1093/jac/dki084.
- [28] B.T. Aftab, I. Dobromilskaya, J.O. Liu and C.M. Rudin, “Itraconazole inhibits angiogenesis and tumor growth in non-small cell lung cancer” Cancer Res, vol. 71(21), pp. 6764-6772, Nov 2011, doi:10.1158/0008-5472.CAN-11-0691.
- [29] E.S. Antonarakis, E.I. Heath, D.C. Smith, D. Rathkopf, A.L. Blackford, D.C. Danila, S. King, A. Frost, A.S. Ajiboye, M. Zhao, J. Mendonca, S.K. Kachhap, M.A. Rudek and M.A. Carducci, “Repurposing itraconazole as a treatment for advanced prostate cancer: a noncomparative randomized phase II trial in men with metastatic castration-resistant prostate cancer,” Oncologist, vol. 18(2), pp. 163-173, Feb 2013, doi:10.1634/theoncologist.2012-314.
- [30] C.R. Chong, J. Xu, J. Lu, S. Bhat, D.J. Jr. Sullivan and J.O. Liu, “Inhibition of Angiogenesis by the Antifungal Drug Itraconazole,” ACS Chem Biol, vol. 2(4), pp. 263-270, Apr 2007, doi:10.1021/cb600362d.
- [31] C.M. Rudin, J.R. Brahmer, R.A. Juergens, C.L. Hann, D.S. Ettinger, R. Sebree, R. Smith, B.T. Aftab, P. Huang and J.O. Liu, “Phase 2 study of pemetrexed and itraconazole as second-line therapy for metastatic nonsquamous non-small-cell lung cancer,” J Thorac Oncol, vol. 8(5), pp. 619-623, May 2013, doi:10.1097/JTO.0b013e31828c3950.