Anticancer effect evaluation in vitro and in vivo of iridium(III) polypyridyl complexes targeting DNA and mitochondria

Zhang, Huiwen; Tian, Li; Xiao, Rongxing; Zhou, Yi; Zhang, Yuanyuan; Hao, Jing; Liu, Yun-Jun; Wang, Juping

doi:10.1016/j.bioorg.2021.105290

Cited by 27 publications

(11 citation statements)

References 81 publications

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“…The SGC-7901 cells were cultured in six-well plates and treated with IC 50 concentrations of 3b and 3c for 24 h. The cells were lysed for 10 min and centrifuged to obtain the supernatant. The prepared ATP detection working solution was added into the supernatant, 5 min late, the RLU value was measured [ 42 ].…”

Section: Methodsmentioning

confidence: 99%

Synthesis, Characterization and Anticancer Efficacy Evaluation of Benzoxanthone Compounds toward Gastric Cancer SGC-7901

Fu¹,

Xu²,

Liu³

et al. 2022

Molecules

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Three benzoxanthone derivatives were synthesized through a new photochemical strategy. The in vitro cytotoxic activity of these compounds was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and their partition coefficients (logP) were measured by shake flask method. The pKa values of the compounds were detected by potentionmetric titration. The interaction of the compounds with calf thymus DNA (CT-DNA) was investigated by electronic absorption, luminescence spectra and viscosity. A molecular docking analysis was performed. The antitumor efficacy of the compounds was evaluated by cell apoptosis, cell cycle arrest, intracellular Ca2+ concentrations and reactive oxygen species (ROS) levels. The mitochondrial membrane potential was assayed using JC-1 (5,5′,6,6′-tetrachloro-1,1,3′,3′-tetraethyl-imidacarbocyanine iodide) as the fluorescence probe. The expression of Bcl-2 family protein, caspase 3 and poly ADP-ribose polymerase (PARP) was explored by western blot. The results showed that the compounds induced apoptosis through a ROS-mediated mitochondrial dysfunction pathway. This work provides an efficient approach to synthesize benzoxanthone derivatives, and is helpful for understanding the apoptotic mechanism.

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Section: Methodsmentioning

confidence: 99%

Synthesis, Characterization and Anticancer Efficacy Evaluation of Benzoxanthone Compounds toward Gastric Cancer SGC-7901

Fu¹,

Xu²,

Liu³

et al. 2022

Molecules

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“…A variety of metal complexes have been developed that not only act on mitochondria but also can bind to DNA ( Figure 4 ), which can cause excessive DNA damage to kill cancer cells, including platinum complexes 26 and 27 [ 112 , 113 ], iridium complex 28 [ 114 ], and copper complex 29 [ 115 ]. Taking 27 as an important example, 27 can interact with DNA through groove binding and has the potential to break DNA [ 113 ].…”

Section: Anti-cancer Metal Complexes Activating Ros-mediated Signaling From Mitochondriamentioning

confidence: 99%

Metal Complexes or Chelators with ROS Regulation Capacity: Promising Candidates for Cancer Treatment

Wang

et al. 2021

Molecules

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Reactive oxygen species (ROS) are rapidly eliminated and reproduced in organisms, and they always play important roles in various biological functions and abnormal pathological processes. Evaluated ROS have frequently been observed in various cancers to activate multiple pro-tumorigenic signaling pathways and induce the survival and proliferation of cancer cells. Hydrogen peroxide (H2O2) and superoxide anion (O2•−) are the most important redox signaling agents in cancer cells, the homeostasis of which is maintained by dozens of growth factors, cytokines, and antioxidant enzymes. Therefore, antioxidant enzymes tend to have higher activity levels to maintain the homeostasis of ROS in cancer cells. Effective intervention in the ROS homeostasis of cancer cells by chelating agents or metal complexes has already developed into an important anti-cancer strategy. We can inhibit the activity of antioxidant enzymes using chelators or metal complexes; on the other hand, we can also use metal complexes to directly regulate the level of ROS in cancer cells via mitochondria. In this review, metal complexes or chelators with ROS regulation capacity and with anti-cancer applications are collectively and comprehensively analyzed, which is beneficial for the development of the next generation of inorganic anti-cancer drugs based on ROS regulation. We expect that this review will provide a new perspective to develop novel inorganic reagents for killing cancer cells and, further, as candidates or clinical drugs.

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“…In addition, cyclometalated iridium(III) and rhenium(I) tricarbonyl complexes have been widely used in bioimaging and biosensing by virtue of their rich photophysical properties, e.g., high quantum yields, large Stokes shifts, long emission lifetimes, high photostability and cell permeability. [5][6][7][8][9][10] Many researchers have confirmed cyclometalated iridium (III) complexes to be promising alternatives to platinum-based drugs, because they possess multiple anticancer modes, such as catalyzing cellular redox reactions, [11][12][13] damaging specific subcellular organelles [14][15][16][17][18] and inhibiting protein activities. 19,20 In addition, the C^N ligands of cyclometalated iridium(III) complexes can effectively regulate their photophysical and photochemical properties, lipophilicities, molecular sizes, and so on.…”

Section: Introductionmentioning

confidence: 99%

“…19,20 In addition, the C^N ligands of cyclometalated iridium(III) complexes can effectively regulate their photophysical and photochemical properties, lipophilicities, molecular sizes, and so on. 16,[20][21][22] Chao et al reported that endoplasmic reticulum-targeted anticancer cyclometalated iridium (III) complexes initiated endoplasmic reticulum stress and induced immunogenic cell death. 23 The cyclometalated iridium(III) complexes synthesized by Liu et al induced apoptosis and autophagy in B16 cells through reactive oxygen species (ROS)-mediated mitochondrial dysfunction and inhibition of the AKT/mTOR pathway.…”

Section: Introductionmentioning

confidence: 99%

Novel heterobimetallic Ir(iii)–Re(i) complexes: design, synthesis and antitumor mechanism investigation

Lu¹,

Ma²,

Xie³

et al. 2022

Dalton Trans.

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Anticancer effect evaluation in vitro and in vivo of iridium(III) polypyridyl complexes targeting DNA and mitochondria

Cited by 27 publications

References 81 publications

Synthesis, Characterization and Anticancer Efficacy Evaluation of Benzoxanthone Compounds toward Gastric Cancer SGC-7901

Synthesis, Characterization and Anticancer Efficacy Evaluation of Benzoxanthone Compounds toward Gastric Cancer SGC-7901

Metal Complexes or Chelators with ROS Regulation Capacity: Promising Candidates for Cancer Treatment

Novel heterobimetallic Ir(iii)–Re(i) complexes: design, synthesis and antitumor mechanism investigation

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