Journal article
Cyclometalated Ru(II) β-carboline complexes induce cell cycle arrest and apoptosis in human HeLa cervical cancer cells via suppressing ERK and Akt signaling
JBIC Journal of Biological Inorganic Chemistry
2021
Abstract
Two new cyclometalated Ru(II)-β-carboline complexes, [Ru(dmb)2(Cl-Ph-βC)](PF6) (dmb = 4,4′-dimethyl-2,2′-bipyridine; Cl-Ph-βC = Cl-phenyl-9H-pyrido[3,4-b]indole; RuβC-3) and [Ru(bpy)2(Cl-Ph-βC)](PF6) (bpy = 2,2′-bipyridine; RuβC-4) were synthesized and characterized. The Ru(II) complexes display high cytotoxicity against HeLa cells, the stabilized human cervical cancer cell, with IC50 values of 3.2 ± 0.4 μM (RuβC-3) and 4.1 ± 0.6 μM (RuβC-4), which were considerably lower than that of non-cyclometalated Ru(II)-β-carboline complex [Ru(bpy)2(1-Py-βC)] (PF6)2 (61.2 ± 3.9 μM) by 19- and 15-folds, respectively. The mechanism studies indicated that both Ru(II) complexes could significantly inhibit HeLa cell migration and invasion, and effectively induce G0/G1 cell cycle arrest. The new Ru(II) complexes could also trigger apoptosis through activating caspase-3 and poly (ADP-ribose) polymerase (PARP), increasing the Bax/Bcl-2 ratio, enhancing reactive oxygen species (ROS) generation, decreasing mitochondrial membrane potential (MMP), and inducing cytochrome c release from mitochondria. Further research revealed that RuβC-3 could deactivate the ERK/Akt signaling pathway thus inhibiting HeLa cell invasion and migration, and inducing apoptosis. In addition, RuβC-3-induced apoptosis in HeLa cells was closely associated with the increase of intracellular ROS levels, which may act as upstream factors to regulate ERK and Akt pathways. More importantly, RuβC-3 exhibited low toxicity on both normal BEAS-2B cells in vitro and zebrafish embryos in vivo. Consequently, the developed Ru(II) complexes have great potential on developing novel low-toxic anticancer drugs.
Details
- Title
- Cyclometalated Ru(II) β-carboline complexes induce cell cycle arrest and apoptosis in human HeLa cervical cancer cells via suppressing ERK and Akt signaling
- Authors/Creators
- J. Chen (Author/Creator) - Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou)Y. Deng (Author/Creator) - Guangdong Medical CollegeJ. Wang (Author/Creator) - Guangdong Medical CollegeS. Chen (Author/Creator) - Murdoch UniversityF. Peng (Author/Creator) - Guangdong Medical CollegeX. He (Author/Creator) - Guangdong Medical CollegeM. Liu (Author/Creator) - Guangdong Medical CollegeH. Luo (Author/Creator) - Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou)J. Zhang (Author/Creator) - The Marine Biomedical Research Institute of Guangdong Zhanjiang, Zhanjiang, ChinaL. Chen (Author/Creator) - Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou)
- Publication Details
- JBIC Journal of Biological Inorganic Chemistry
- Publisher
- Springer Nature
- Identifiers
- 991005542030207891
- Copyright
- © 2021 Springer Nature Switzerland AG.
- Murdoch Affiliation
- Centre for Molecular Medicine and Innovative Therapeutics
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 2 Chemistry
- 2.22 Inorganic & Nuclear Chemistry
- 2.22.798 Metal Anticancer Complexes
- Web Of Science research areas
- Biochemistry & Molecular Biology
- Chemistry, Inorganic & Nuclear
- ESI research areas
- Chemistry