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Imidazole Antifungals: A Review of Their Action Mechanisms on Cancerous Cells

Yıl 2020, Cilt: 7 Sayı: 3, 139 - 159, 15.09.2020
https://doi.org/10.21448/ijsm.714310

Öz

Imidazoles, together with triazoles, constitute azole sub-group of antifungal drugs which acts by inhibiting cytochrome P450-dependent enzyme, the lanosterol 14-α-demethylase. In addition to their primary use, when it comes to additional anti-cancer function, clotrimazole, econazole and ketoconazole have come to the fore among the imidazoles. Based on the findings up to now, although having different effects, disruption of the glycolytic pathway, blockage of Ca2+ influx and nonspecific inhibition of CYP450 enzymes can be regarded as the main ones responsible for the anti-neoplastic activities of the mentioned drugs, respectively. Considering the advantages of repurposing of drugs with known pharmacology compared to new drug development studies requiring labor, time and cost, it will be extremely important and valuable to continue the clarification of the different mechanisms of these antifungals on cancerous cells and benefit from them especially to increase drug efficacy and overcome drug resistance. In this review, the action mechanisms of imidazole antifungals on cancerous cells and consequently, their potential for use in cancer treatment alone or in combination with conventional therapeutics were discussed in detail.

Kaynakça

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Imidazole Antifungals: A Review of Their Action Mechanisms on Cancerous Cells

Yıl 2020, Cilt: 7 Sayı: 3, 139 - 159, 15.09.2020
https://doi.org/10.21448/ijsm.714310

Öz

Imidazoles, together with triazoles, constitute azole sub-group of antifungal drugs which acts by inhibiting cytochrome P450-dependent enzyme, the lanosterol 14-α-demethylase. In addition to their primary use, when it comes to additional anti-cancer function, clotrimazole, econazole and ketoconazole have come to the fore among the imidazoles. Based on the findings up to now, although having different effects, disruption of the glycolytic pathway, blockage of Ca2+ influx and nonspecific inhibition of CYP450 enzymes can be regarded as the main ones responsible for the anti-neoplastic activities of the mentioned drugs, respectively. Considering the advantages of repurposing of drugs with known pharmacology compared to new drug development studies requiring labor, time and cost, it will be extremely important and valuable to continue the clarification of the different mechanisms of these antifungals on cancerous cells and benefit from them especially to increase drug efficacy and overcome drug resistance. In this review, the action mechanisms of imidazole antifungals on cancerous cells and consequently, their potential for use in cancer treatment alone or in combination with conventional therapeutics were discussed in detail.

Kaynakça

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  • Huang, H., Wang, H., Sinz, M., Zoeckler, M., Staudinger, J., Redinbo, M.R., Teotico, D.G., Locker, J., Kalpana, G.V., Mani, S. (2007). Inhibition of drug metabolism by blocking the activation of nuclear receptors by ketoconazole. Oncogene, 26(2), 258.
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  • Kast, R.E., Boockvar, J.A., Brüning, A., Cappello, F., Chang, W.W., Cvek, B., Ping Dou, Q., Duenas-Gonzalez, A., Efferth, T., Focosi, D., Ghaffari, S.H., Karpel-Massler, G., Ketola, K., Khoshnevisan, A., Keizman, D., Magné, N., Marosi, C., McDonald, K., Muñoz, M., Paranjpe, A., Pourgholami, M.H., Sardi, L., Sella, A., Srivenugopal, K.S., Tuccori, M., Wang, W., Wirtz, C.R., Halatsch, M.E. (2013). A conceptually new treatment approach for relapsed glioblastoma: coordinated undermining of survival paths with nine repurposed drugs (CUSP9) by the International Initiative for Accelerated Improvement of Glioblastoma Care. Oncotarget, 4(4), 502.
  • Agarwal, S.K., Salem, A.H., Danilov, A.V., Hu, B., Puvvada, S., Gutierrez, M., Chien, D., Lewis, L.D., Wong, S.L. (2017). Effect of ketoconazole, a strong CYP3A inhibitor, on the pharmacokinetics of venetoclax, a BCL‐2 inhibitor, in patients with non‐Hodgkin lymphoma. Br. J. Clin. Pharmacol., 83(4), 846-854.
  • Cheng, J.S., Chou, C.T., Liang, W.Z., Kuo, C.C., Shieh, P., Kuo, D.H., Jan, C.R. (2014). The mechanism of bifonazole-induced [Ca2+]i rises and non-Ca2+-triggered cell death in PC3 human prostate cancer cells. J. Recept. Sig. Transd., 34(6), 493-499.
  • Robey, R.W., McDonald, A.J., Kozlowski, H., Gottesman, M.M., Bates, S.E. Short-Term Romidepsin Treatment Combined with Clotrimazole or Bifonazole Leads to Decreased Mitochondrial Hexokinase 2 and Apoptosis in Cancer Cells In: Proceedings of the American Association for Cancer Research Annual Meeting, Washington, DC., Philadelphia, April 1-5, 2017, doi:10.1158/1538-7445.AM2017-4040.
  • Bruserud, O. (2001). Effects of azoles on human acute myelogenous leukemia blasts and T lymphocytes derived from acute leukemia patients with chemotherapy-induced cytopenia. Int. Immunopharmacol., 1(12), 2183-2195.
  • Yuan, S.Y., Shiau, M.Y., Ou, Y.C., Huang, Y.C., Chen, C.C., Cheng, C.L., Chiu, K.Y., Wang, S.S., Tsai, K.J. (2017). Miconazole induces apoptosis via the death receptor 5-dependent and mitochondrial-mediated pathways in human bladder cancer cells. Oncol. Rep., 37(6), 3606-3616.
  • Shahbazfar, A.A., Zare, P., Ranjbaran, M., Tayefi-Nasrabadi, H., Fakhri, O., Farshi, Y., Shadi, S., Khoshkerdar, A. (2014). A survey on anticancer effects of artemisinin, iron, miconazole, and butyric acid on 5637 (bladder cancer) and 4T1 (Breast cancer) cell lines. J. Cancer Res. Ther., 10(4), 1057.
  • Wu, C.H., Jeng, J.H., Wang, Y.J., Tseng, C.J., Liang, Y.C., Chen, C.H., Lee, H.M., Lin, J.K., Lin, C.H., Lin, S.Y., Li, C.P., Ho, Y.S. (2002). Antitumor effects of miconazole on human colon carcinoma xenografts in nude mice through induction of apoptosis and G0/G1 cell cycle arrest. Toxicol. Appl. Pharm., 180(1), 22-35.
  • Mun, Y.J., Lee, S.W., Jeong, H.W., Lee, K.G., Kim, J.H., Woo, W.H. (2004). Inhibitory effect of miconazole on melanogenesis. Biol. Pharm. Bull., 27(6), 806-809.
  • Lee, K.P., Kim, J.E., Park, W.H. (2015). Cytoprotective effect of rhamnetin on miconazole-induced H9c2 cell damage. Nutr. Res. Pract., 9(6), 586-591.
  • Won, K.J., Lin, H.Y., Jung, S., Cho, S.M., Shin, H.C., Bae, Y.M., Lee, S.H., Kim, H.J., Jeon, B.H., Kim, B. (2012). Antifungal miconazole induces cardiotoxicity via inhibition of APE/Ref-1-related pathway in rat neonatal cardiomyocytes. Toxicol. Sci., 126(2), 298-305.
  • Ashbee, H.R., Gilleece, M.H. (2014). Pharmacogenomics of Antifungal Agents In: Handbook of Pharmacogenomics and Stratified Medicine, Sandosh Padmanabhan, Ed. Academic Press, pp. 879-896.
  • Dash, A.K., & Elmquist, W.F. (2001). Fluconazole In: Profiles of Drug Substances, Excipients and Related Methodology, HG Brittain, Academic Press: San Diego, 27, 67-113.
  • Le, A., Farmakiotis, D., Tarrand, J.J., Kontoyiannis, D.P. (2017). Initial treatment of cancer patients with fluconazole-susceptible dose-dependent Candida glabrata fungemia: better outcome with an echinocandin or polyene compared to an azole? Antimicrob. Agents Chemother., 61(8), e00631-17.
  • da Silva, C.R., de Andrade Neto, J.B., de Sousa Campos, R., Figueiredo, N.S., Sampaio, L.S., Magalhães, H.I.F., Cavalcanti, B.C., Gaspar, D.M., de Andrade, G.M., Lima, I.S.P., de Barros Viana, G.S., de Moraes, M.O., Lobo, M.D.P., Grangeiro, T.B., Júnior, H.V.N. (2014). Synergistic effect of the flavonoid catechin, quercetin, or epigallocatechin gallate with fluconazole induces apoptosis in Candida tropicalis resistant to fluconazole. Antimicrob. Agents Chemother., 58(3), 1468-1478.
  • Singh, B.N., Upreti, D.K., Singh, B.R., Pandey, G., Verma, S., Roy, S., Naqvi, A.H., Rawat, A.K.S. (2015). Quercetin sensitizes fluconazole-resistant Candida albicans to induce apoptotic cell death by modulating quorum sensing. Antimicrob. Agents Chemother., 59(4), 2153-2168.
  • Wang, X., Wei, S., Zhao, Y., Shi, C., Liu, P., Zhang, C., Lei, Y., Zhang, B., Bai, B., Huang, Y., Zhang, H. (2017). Anti-proliferation of breast cancer cells with itraconazole: Hedgehog pathway inhibition induces apoptosis and autophagic cell death. Cancer Lett., 385, 128-136.
  • Hu, Q., Hou, Y.C., Huang, J., Fang, J.Y., Xiong, H. (2017). Itraconazole induces apoptosis and cell cycle arrest via inhibiting Hedgehog signaling in gastric cancer cells. J. Exp. Clin. Canc. Res., 36(1), 50.
  • Liu, R., Li, J., Zhang, T., Zou, L., Chen, Y., Wang, K., Lei, Y., Yuan, K., Li, Y., Lan, J., Cheng, L., Xie, N., Xiang, R., Nice, E.C., Huang, C., Wei, Y. (2014). Itraconazole suppresses the growth of glioblastoma through induction of autophagy: involvement of abnormal cholesterol trafficking. Autophagy, 10(7), 1241-1255.
  • Chen, M.B., Liu, Y.Y., Xing, Z.Y., Zhang, Z.Q., Jiang, Q., Lu, P.H., Cao, C. (2018). Itraconazole-induced inhibition on human esophageal cancer cell growth requires AMPK activation. Mol. Cancer Ther., 17(6), 1229-1239.
  • Liang, G., Liu, M., Wang, Q., Shen, Y., Mei, H., Li, D., Liu, W. (2017). Itraconazole exerts its anti-melanoma effect by suppressing Hedgehog, Wnt, and PI3K/mTOR signaling pathways. Oncotarget, 8(17), 28510.
  • Hara, M., Nagasaki, T., Shiga, K., Takeyama, H. (2016). Suppression of cancer-associated fibroblasts and endothelial cells by itraconazole in bevacizumab-resistant gastrointestinal cancer. Anticancer Res., 36(1), 169-177.
  • Aftab, B.T., Dobromilskaya, I., Liu, J.O., Rudin, C.M. (2011). Itraconazole inhibits angiogenesis and tumor growth in non–small cell lung cancer. Cancer Res., 71(21), 6764-6772.
  • Wang, J., Xu, X., Zhou, R., Guo, K. (2015). Effects of itraconazole plus doxorubicin on proliferation and apoptosis in acute myeloid leukemia cells. Chin. J. Cancer, 95(4), 299-305.
  • Sari, I.N., Phi, L.T.H., Jun, N., Wijaya, Y.T., Lee, S., Kwon, H.Y. (2018). Hedgehog signaling in cancer: a prospective therapeutic target for eradicating cancer stem cells. Cells, 7(11), 208.
  • Tsubamoto, H., Ueda, T., Inoue, K., Sakata, K., Shibahara, H., Sonoda, T. (2017). Repurposing itraconazole as an anticancer agent. Oncology letters, 14(2), 1240-1246.
  • Peyton, L.R., Gallagher, S., Hashemzadeh, M. (2015). Triazole antifungals: a review. Drug. Today (Barc), 51(12), 705-718.
  • Choi, S.H., Lee, S.Y., Hwang, J.Y., Lee, S.H., Yoo, K.H., Sung, K.W., Koo, H.H., Kim, Y.J. (2013). Importance of voriconazole therapeutic drug monitoring in pediatric cancer patients with invasive aspergillosis. Pediatr. Blood Cancer, 60(1), 82-87.
  • Pham, A.N., Bubalo, J.S., Lewis, J.S. (2016). Comparison of posaconazole serum concentrations from haematological cancer patients on posaconazole tablet and oral suspension for treatment and prevention of invasive fungal infections. Mycoses, 59(4), 226-233.
  • Takahashi, H., Abe, M., Sugawara, T., Tanaka, K., Saito, Y., Fujimura, S., Shibuya, M., Sato, Y. (1998). Clotrimazole, an imidazole antimycotic, is a potent inhibitor of angiogenesis. Jpn. J. Clin. Oncol., 89(4), 445-451.
  • Khalid, M.H., Shibata, S., Hiura, T. (1999). Effects of clotrimazole on the growth, morphological characteristics, and cisplatin sensitivity of human glioblastoma cells in vitro. J. Neurosurg., 90(5), 918-927.
  • Khalid, M.H., Shibata, S., Hiura, T. (1999). Effects of clotrimazole on the growth, morphological characteristics, and cisplatin sensitivity of human glioblastoma cells in vitro. J. Neurosurg., 90(5), 918-927.
  • Adinolfi, B., Carpi, S., Romanini, A., Da Pozzo, E., Castagna, M., Costa, B., Martini, C., Olesen, S.P., Schmitt, N., Breschi, M.C., Nieri, P., Fogli, S. (2015). Analysis of the antitumor activity of clotrimazole on A375 human melanoma cells. Anticancer Res., 35(7), 3781-3786.
  • McDonald, A.J., Curt, K.M., Patel, R.P., Kozlowski, H., Sackett, D.L., Robey, R.W., Gottesman, M.M., Bates, S.E. (2019). Targeting mitochondrial hexokinases increases efficacy of histone deacetylase inhibitors in solid tumor models. Exp. Cell Res., 375(2), 106-112.
  • Dong, C., Yang, R., Li, H., Ke, K., Luo, C., Yang, F., Shi, X.N., Zhu, Y., Liu, X., Wong, M.H., Lin, G., Wang, X., Leung, K.S., Kung, H.F., Chen, C., Lin, M.C. (2017). Econazole nitrate inhibits PI3K activity and promotes apoptosis in lung cancer cells. Sci. Rep., 7(1), 17987.
  • Rochlitz, C.F., Damon, L.E., Russi, M.B., Geddes, A., Cadman, E.C. (1988). Cytotoxicity of ketoconazole in malignant cell lines. Cancer Chemother. Pharmacol., 21(4), 319-322.
  • Lu, C.T., Leong, P.Y., Hou, T.Y., Kang, Y.T., Chiang, Y.C., Hsu, C.T., Lin, Y.D., Ko, J.L., Hsiao, Y.P. (2019). Inhibition of proliferation and migration of melanoma cells by ketoconazole and Ganoderma immunomodulatory proteins. Oncol. Lett., 18(1), 891-897.
Toplam 135 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Yapısal Biyoloji
Bölüm Makaleler
Yazarlar

Berna Kavakcıoğlu Yardımcı 0000-0003-0719-9094

Yayımlanma Tarihi 15 Eylül 2020
Gönderilme Tarihi 3 Nisan 2020
Yayımlandığı Sayı Yıl 2020 Cilt: 7 Sayı: 3

Kaynak Göster

APA Kavakcıoğlu Yardımcı, B. (2020). Imidazole Antifungals: A Review of Their Action Mechanisms on Cancerous Cells. International Journal of Secondary Metabolite, 7(3), 139-159. https://doi.org/10.21448/ijsm.714310
International Journal of Secondary Metabolite
e-ISSN: 2148-6905