Phosphorescent rhenium(I) complexes conjugated with artesunate: Mitochondrial targeting and apoptosis-ferroptosis dual induction

Ye, Rui-Rong; Chen, Bi-Chun; Lu, Junjian; Ma, Xiu-Rong; Li, Rong‐Tao

doi:10.1016/j.jinorgbio.2021.111537

Cited by 31 publications

(21 citation statements)

References 63 publications

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“…SGC-7901 cells were incubated with IC 50 concentrations of 3b and 3c for 24 h. Afterwards, the cells were lysed by the freeze-thaw method, and the lysate was centrifuged for 5 min to collect the supernatant. The absorbance was measured at 412 nm with a microplate reader [ 39 ].…”

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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“…While inhibition of HSPB1 expression increases the anticancer activity of erastin in cervical cancer ( Sun et al, 2015 ). In addition, researchers designed two artesunate-conjugated phosphorescence rhenium (I) complexes, which can induce both apoptosis and ferroptosis of cervical cancer cells by glutathione depletion, GPX4 inactivation and lipid peroxidation accumulation, improving the treatment efficiency ( Ye et al, 2021 ). Further exploration of the mechanism of ferroptosis in cervical cancer may be significant for cervical cancer progression and treatment.…”

Section: Ferroptosis In Gynecological Malignanciesmentioning

confidence: 99%

New Insights on Ferroptosis and Gynecological Malignancies

Fan

Sun

Wang

et al. 2022

Front. Mol. Biosci.

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Ferroptosis is a new type of cell death different from apoptosis and necrosis, which can regulate the accumulation of lipid peroxidation through different pathways, ultimately leading to cell death. An increasing number of studies have revealed that the relationship between ferroptosis and cancer is extremely complex, which holds promise as a new treatment. In gynecological malignancies, ferroptosis has been found to have excellent antitumor activity, which can regulate the proliferation, metastasis and radiochemotherapy resistance. With the continuous progress of research, nanodrugs, gene therapy and other new therapeutic techniques for inducing ferroptosis have been proposed. However, the study of ferroptosis in gynecological malignancies is still in its infancy, and further research is needed to design safe and effective cancer therapies based on ferroptosis. This article reviews the mechanism of ferroptosis and the latest research progress and prospects in gynecological malignancies.

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“…Recently, many other metal complexes targeting mitochondria have also been developed to kill cancer cells by regulating the level of intracellular ROS ( Figure 4 ), such as copper complexes 21 and 22 [ 107 , 108 ], rhodium complex 23 [ 109 ], gold complex 24 [ 110 ], and rhenium complex 25 [ 111 ]. Interestingly, 24 is also a necroptosis inducer and a potential option in cases of apoptosis resistance; it disrupts the normal function of mitochondria, leading to ROS elevation in colorectal adenocarcinoma cells [ 110 ].…”

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

confidence: 99%

“…Interestingly, 24 is also a necroptosis inducer and a potential option in cases of apoptosis resistance; it disrupts the normal function of mitochondria, leading to ROS elevation in colorectal adenocarcinoma cells [ 110 ]. Another thing worth mentioning is that rhenium complex 25 can induce both apoptosis and ferroptosis in cancer cells through mitochondrial dysfunction, caspase cascade, glutathione depletion, glutathione peroxidase 4 inactivation, and lipid peroxidation, which is a promising strategy to induce both apoptosis and ferroptosis at the same time [ 111 ].…”

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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Phosphorescent rhenium(I) complexes conjugated with artesunate: Mitochondrial targeting and apoptosis-ferroptosis dual induction

Cited by 31 publications

References 63 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

New Insights on Ferroptosis and Gynecological Malignancies

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

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