Erkan Kahraman1,2, Erdem Göker3,4. 1. Research and Application Center of Individualized Medicine, Ege University, Izmir, Turkey. 2. Atatürk Vocational School of Health Services, Ege University, Izmir, Turkey. 3. Research and Application Center of Individualized Medicine, Ege University, Izmir, Turkey. erdem.goker@ege.edu.tr. 4. Medical Oncology, Faculty of Medicine, Ege University, Izmir, Turkey. erdem.goker@ege.edu.tr.
Abstract
BACKGROUND: Imidazole nucleus has been used efficiently in the development of many drug molecules due to its therapeutic effects. Many derivatives of it have been produced particularly for use in cancer treatment. However, the anti-cancer effects of imidazole nucleus in liver cancer cells are as yet unclear. In this study, we aimed to investigate the anti-cancer effects of imidazole nucleus in hepatocellular carcinoma (HCC) cell lines. METHODS AND RESULTS: Anti-cancer effect of imidazole nucleus was investigated using cell viability assay, apoptosis analysis, cell migration analysis, cell morphology analysis, colony formation assay and 3D cell culture techniques in HuH-7 and Mahlavu cell lines. Also, effect of imidazole on AKT and ERK1/2 pathways were determined using by western blot analysis. Imidazole decreased cell viability in both HCC cell lines in a dose and time-dependent manner and also suppressed the colony forming ability of the cells (p < 0.05). Imidazole increased the cleaved caspase 3 protein levels and thus induced apoptosis (p < 0.05). Imidazole induced morphological alterations and autophagy by increasing intracellular vacuolization. Also, imidazole decreased the viability and dimensions of HCC cell tumor spheroids produced in 3D cell cultures (p < 0.05). Moreover, it was observed that all of these effects, are defined above, appeared in parallel with suppression of AKT and ERK1/2 signaling pathways by imidazole nucleus. CONCLUSIONS: The findings of this present study established the anti-cancer effects of imidazole nucleus in HCC cell lines and showed that it could be a potential molecule in the treatment of HCC via inhibition of AKT and ERK1/2 signaling pathways.
BACKGROUND: Imidazole nucleus has been used efficiently in the development of many drug molecules due to its therapeutic effects. Many derivatives of it have been produced particularly for use in cancer treatment. However, the anti-cancer effects of imidazole nucleus in liver cancer cells are as yet unclear. In this study, we aimed to investigate the anti-cancer effects of imidazole nucleus in hepatocellular carcinoma (HCC) cell lines. METHODS AND RESULTS: Anti-cancer effect of imidazole nucleus was investigated using cell viability assay, apoptosis analysis, cell migration analysis, cell morphology analysis, colony formation assay and 3D cell culture techniques in HuH-7 and Mahlavu cell lines. Also, effect of imidazole on AKT and ERK1/2 pathways were determined using by western blot analysis. Imidazole decreased cell viability in both HCC cell lines in a dose and time-dependent manner and also suppressed the colony forming ability of the cells (p < 0.05). Imidazole increased the cleaved caspase 3 protein levels and thus induced apoptosis (p < 0.05). Imidazole induced morphological alterations and autophagy by increasing intracellular vacuolization. Also, imidazole decreased the viability and dimensions of HCC cell tumor spheroids produced in 3D cell cultures (p < 0.05). Moreover, it was observed that all of these effects, are defined above, appeared in parallel with suppression of AKT and ERK1/2 signaling pathways by imidazole nucleus. CONCLUSIONS: The findings of this present study established the anti-cancer effects of imidazole nucleus in HCC cell lines and showed that it could be a potential molecule in the treatment of HCC via inhibition of AKT and ERK1/2 signaling pathways.
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Authors: Adriana Valls; Jose J Andreu; Eva Falomir; Santiago V Luis; Elena Atrián-Blasco; Scott G Mitchell; Belén Altava Journal: Pharmaceuticals (Basel) Date: 2020-12-21