Ru(II) Complexes Bearing O, O-Chelated Ligands Induced Apoptosis in A549 Cells through the Mitochondrial Apoptotic Pathway
Two new Ru(II) complexes containing O, O-chelated ligands, Ru(dip)2(SA) (Ru-1) and Ru(dmp)2(SA) (Ru-2) (dip = 4,7-diphenyl-1,10-phenanthroline; dmp = 2,9-dimethyl-1,10-phenanthroline; SA = salicylate) were synthesized to evaluate their cytotoxicity in vitro. These complexes were found to exhibit mod...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Bioinorganic Chemistry and Applications |
| Online Access: | http://dx.doi.org/10.1155/2020/8890950 |
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| author | Jincan Chen Jie Wang Yuanyuan Deng Tao Wang Tifang Miao Chengpeng Li Xianhong Cai Ying Liu Justin Henri Lanmei Chen |
| author_facet | Jincan Chen Jie Wang Yuanyuan Deng Tao Wang Tifang Miao Chengpeng Li Xianhong Cai Ying Liu Justin Henri Lanmei Chen |
| author_sort | Jincan Chen |
| collection | DOAJ |
| description | Two new Ru(II) complexes containing O, O-chelated ligands, Ru(dip)2(SA) (Ru-1) and Ru(dmp)2(SA) (Ru-2) (dip = 4,7-diphenyl-1,10-phenanthroline; dmp = 2,9-dimethyl-1,10-phenanthroline; SA = salicylate) were synthesized to evaluate their cytotoxicity in vitro. These complexes were found to exhibit moderate antitumor activity to different types of human cancers, including A549 (human lung carcinoma), MCF-7 (breast cancer), HeLa (human cervical cancer), and HepG2 (human hepatocellular carcinoma) cell lines, but displayed low toxicity to human normal cell lines BEAS-2B (immortalized human bronchial epithelial cells) when compared with that of cisplatin. Further studies revealed that these complexes could induce apoptosis in A549 cells, including activating caspase family proteins and poly (ADP-ribose) polymerase (PARP), reducing Bcl-2/Bax and Bcl-xl/Bad ratio, enhancing cellular reactive oxygen species (ROS) accumulation, triggering DNA damage, decreasing mitochondrial membrane potential (MMP), and leading cytochrome c release from mitochondria. Notably, complex Ru-1 showed low toxicity to developing zebrafish embryos. The obtained results suggest that these new synthetic complexes have the potential to be developed as low-toxicity agents for lung cancer treatment. |
| format | Article |
| id | doaj-art-e8529004ecdb4139a703661d47e01b89 |
| institution | Kabale University |
| issn | 1565-3633 1687-479X |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
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| series | Bioinorganic Chemistry and Applications |
| spelling | doaj-art-e8529004ecdb4139a703661d47e01b892025-02-03T01:24:56ZengWileyBioinorganic Chemistry and Applications1565-36331687-479X2020-01-01202010.1155/2020/88909508890950Ru(II) Complexes Bearing O, O-Chelated Ligands Induced Apoptosis in A549 Cells through the Mitochondrial Apoptotic PathwayJincan Chen0Jie Wang1Yuanyuan Deng2Tao Wang3Tifang Miao4Chengpeng Li5Xianhong Cai6Ying Liu7Justin Henri8Lanmei Chen9Guangdong Key Laboratory for Research and Development of Nature Drugs, Marine Biomedical Research Institute, School of Pharmacy, Guangdong Medical University, Zhanjiang 524023, ChinaGuangdong Key Laboratory for Research and Development of Nature Drugs, Marine Biomedical Research Institute, School of Pharmacy, Guangdong Medical University, Zhanjiang 524023, ChinaGuangdong Key Laboratory for Research and Development of Nature Drugs, Marine Biomedical Research Institute, School of Pharmacy, Guangdong Medical University, Zhanjiang 524023, ChinaSchool of Nursing, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Chemistry and Materials Science, Huaibei Normal University, Huaibei 235000, ChinaThe Public Service Platform of South China Sea for R&D Marine Biomedicine Resources, Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, ChinaGuangdong Key Laboratory for Research and Development of Nature Drugs, Marine Biomedical Research Institute, School of Pharmacy, Guangdong Medical University, Zhanjiang 524023, ChinaGuangdong Key Laboratory for Research and Development of Nature Drugs, Marine Biomedical Research Institute, School of Pharmacy, Guangdong Medical University, Zhanjiang 524023, ChinaSchool of Medicine Deakin University, Geelong, Victoria 3128, AustraliaGuangdong Key Laboratory for Research and Development of Nature Drugs, Marine Biomedical Research Institute, School of Pharmacy, Guangdong Medical University, Zhanjiang 524023, ChinaTwo new Ru(II) complexes containing O, O-chelated ligands, Ru(dip)2(SA) (Ru-1) and Ru(dmp)2(SA) (Ru-2) (dip = 4,7-diphenyl-1,10-phenanthroline; dmp = 2,9-dimethyl-1,10-phenanthroline; SA = salicylate) were synthesized to evaluate their cytotoxicity in vitro. These complexes were found to exhibit moderate antitumor activity to different types of human cancers, including A549 (human lung carcinoma), MCF-7 (breast cancer), HeLa (human cervical cancer), and HepG2 (human hepatocellular carcinoma) cell lines, but displayed low toxicity to human normal cell lines BEAS-2B (immortalized human bronchial epithelial cells) when compared with that of cisplatin. Further studies revealed that these complexes could induce apoptosis in A549 cells, including activating caspase family proteins and poly (ADP-ribose) polymerase (PARP), reducing Bcl-2/Bax and Bcl-xl/Bad ratio, enhancing cellular reactive oxygen species (ROS) accumulation, triggering DNA damage, decreasing mitochondrial membrane potential (MMP), and leading cytochrome c release from mitochondria. Notably, complex Ru-1 showed low toxicity to developing zebrafish embryos. The obtained results suggest that these new synthetic complexes have the potential to be developed as low-toxicity agents for lung cancer treatment.http://dx.doi.org/10.1155/2020/8890950 |
| spellingShingle | Jincan Chen Jie Wang Yuanyuan Deng Tao Wang Tifang Miao Chengpeng Li Xianhong Cai Ying Liu Justin Henri Lanmei Chen Ru(II) Complexes Bearing O, O-Chelated Ligands Induced Apoptosis in A549 Cells through the Mitochondrial Apoptotic Pathway Bioinorganic Chemistry and Applications |
| title | Ru(II) Complexes Bearing O, O-Chelated Ligands Induced Apoptosis in A549 Cells through the Mitochondrial Apoptotic Pathway |
| title_full | Ru(II) Complexes Bearing O, O-Chelated Ligands Induced Apoptosis in A549 Cells through the Mitochondrial Apoptotic Pathway |
| title_fullStr | Ru(II) Complexes Bearing O, O-Chelated Ligands Induced Apoptosis in A549 Cells through the Mitochondrial Apoptotic Pathway |
| title_full_unstemmed | Ru(II) Complexes Bearing O, O-Chelated Ligands Induced Apoptosis in A549 Cells through the Mitochondrial Apoptotic Pathway |
| title_short | Ru(II) Complexes Bearing O, O-Chelated Ligands Induced Apoptosis in A549 Cells through the Mitochondrial Apoptotic Pathway |
| title_sort | ru ii complexes bearing o o chelated ligands induced apoptosis in a549 cells through the mitochondrial apoptotic pathway |
| url | http://dx.doi.org/10.1155/2020/8890950 |
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