Phenanthroimidazole derivatives act as potent inducer of autophagy by activating DNA damage pathway |
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| Affiliation: | 1. The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510006, PR China;2. School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China;3. Guangdong Province Engineering Technology Centre for Molecular Probe and Biomedicine Imagining, Guangzhou 510006, PR China;4. Guangzhou Key Laboratory of Construction and Application of New Drug Screening Model Systems, Guangdong Pharmaceutical University, Guangzhou 510006, China;1. Program of Molecular Medicine, Affiliated Guangzhou Women and Children''s Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China;2. Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, Guangdong Province, China;3. The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China;4. School of Public Health, SUN Yat-Sen University, Guangzhou, 510006, China;5. Guangdong Provincial Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, 510663, China;6. School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, Guangdong, China;1. Key Laboratory of Preparation and Application of Environmental Friendly Materials (Jilin Normal University), Ministry of Education, Changchun 130103, PR China;2. School of Environmental Science and Engineering, Chang’an University, Xi’an 710054, PR China;3. College of Chemistry, Jilin Normal University, Siping 136000, PR China;4. Institute of Green Chemistry & Chemical Technology, Jiangsu University, Zhenjiang 212013, PR China;1. Department of Chemistry, M. V. Lomonosov Moscow State University, Leninskie Gory, 119992 Moscow, Russia;2. A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 28 Vavilova Str., 119991 Moscow, Russia;3. Aix Marseille Université, CNRS, CINaM UMR 7325, Campus de Luminy, Case 913, Marseille 13288, France;1. Department of Biochemistry, Molecular Cancer Research Center, School of Medicine, Sun Yat-sen University, Shenzhen, 518107, Guangdong Province, China;2. Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translation Research of Hakka Population, Meizhou, 514000, Guangdong Province, China;3. Meizhou People''s Hospital, Meizhou, 514000, Guangdong Province, China;4. The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong Province, China;5. School of Public Health, Sun Yat-sen University, Guangzhou, 510080, Guangdong Province, China;6. School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510080, Guangdong Province, China;7. Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, 515041, China;8. Medical Informatics Research Center, Shantou University Medical College, Shantou, 515041, China |
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| Abstract: | A series of imidazo[4,5f][1,10]phenanthroline derivatives (1–6) have been synthesized in this study, and their inhibitory activity was evaluated by MTT assay. Results showed that all of these compounds demonstrate a promising inhibitory activity against a panel of human cancer cell lines. The 6, the most effective compound with IC50 of approximately 2.3 ± 0.1 µM, was against the growth and could induce autophagy of HepG2 cells. This condition was confirmed by abundant autophagic vacuoles appearing in cells and evident ultrastructural changes observed under transmission electron microscopy. The autophage induced by 6 has also been demonstrated by up-regulating LC3-II and Beclin1. The apoptosis and G2/M phase cell cycle arrest through DSB damage have also been confirmed after the HepG2 cells were treated by 6. These multiple effects, especially induction apoptosis and autophagy, indicate the potential of 6 for development as a novel anticancer drug. |
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| Keywords: | Hepatocellular carcinoma Autophagy Apoptosis Inducer Phenanthroline derivative DNA damage Zebrafish |
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