Osmium(<scp>vi</scp>) nitride triggers mitochondria-induced oncosis and apoptosis

Ye, Meng; Huang, Wan-Qiong; Li, Zi-Xin; Wang, Chuanxian; Liu, Tao; Chen, Yunzhou; Hor, Catherine Hong Huan; Man, Wai‐Lun; Ni, Wen‐Xiu

doi:10.1039/d1cc05148b

Cited by 7 publications

(4 citation statements)

References 42 publications

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“…In 2018, a family of cyclometalated iridium(III) compounds bearing benzothiazole ligands were reported for the first time as inducers of a novel, non-apoptotic type of cell death known as oncosis [7]. Recently, an osmium(IV) nitride compound was also found to elicit oncosis in cancer cells [8]. Oncosis (from Greek ónkos, meaning "swelling") refers to a cell death process related to energy depletion [9,10].…”

Section: Introductionmentioning

confidence: 99%

Potent anticancer activity of a novel iridium metallodrug via oncosis

Ortega-Forte

Hernández-García

Vigueras

et al. 2022

Cell. Mol. Life Sci.

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Oncosis (from Greek ónkos, meaning “swelling”) is a non-apoptotic cell death process related to energy depletion. In contrast to apoptosis, which is the main form of cell death induced by anticancer drugs, oncosis has been relatively less explored but holds potential to overcome drug resistance phenomena. In this study, we report a novel rationally designed mitochondria-targeted iridium(III) complex (OncoIr3) with advantageous properties as a bioimaging agent. OncoIr3 exhibited potent anticancer activity in vitro against cancer cells and displayed low toxicity to normal dividing cells. Flow cytometry and fluorescence-based assays confirmed an apoptosis-independent mechanism involving energy depletion, mitochondrial dysfunction and cellular swelling that matched with the oncotic process. Furthermore, a Caenorhabditis elegans tumoral model was developed to test this compound in vivo, which allowed us to prove a strong oncosis-derived antitumor activity in animals (with a 41% reduction of tumor area). Indeed, OncoIr3 was non-toxic to the nematodes and extended their mean lifespan by 18%. Altogether, these findings might shed new light on the development of anticancer metallodrugs with non-conventional modes of action such as oncosis, which could be of particular interest for the treatment of apoptosis-resistant cancers. Graphical abstract

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Section: Introductionmentioning

confidence: 99%

Potent anticancer activity of a novel iridium metallodrug via oncosis

Ortega-Forte

Hernández-García

Vigueras

et al. 2022

Cell. Mol. Life Sci.

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“…Intracellular reactive oxygen species (ROS) oxidative stress can induce cell apoptosis. 18,19 We determined the ROS levels in 6-treated cells by inverted fluorescence microscope and flow cytometry with 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) stained. In the presence of cellular ROS, DCFH-DA can be converted to DCF, which displays green fluorescence.…”

Section: Dalton Transactions Accepted Manuscriptmentioning

confidence: 99%

Cytotoxic cis-ruthenium(iii) bis(amidine) complexes

et al. 2023

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“…The clinical success of platinum-based anticancer drugs such as cisplatin, carboplatin, and oxaliplatin has stimulated extensive investigations into new metallodrugs with improved pharmacological properties, which may reduce side effects, such as kidney toxicity and nausea, and overcome drug resistance [ 2 , 3 , 4 ]. Recently, other metal-based compounds with potential anti-cancer properties have been reported [ 5 , 6 ]. Ruthenium compounds are a potential alternative to platinum-based drugs owing to their chemical and pharmacological properties.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, we reported a new osmium(VI) nitrido complex bearing a nonplanar tetradentate ligand with potent anticancer activity. It causes mitochondrial damage and induces liver cancer cell bimodal death via oncosis and apoptosis [ 5 ]. Lippard et al found that the cellular response evoked by anti-proliferating osmium(VI) nitrido compounds with bidentate lipophilic N,N-chelating ligands could be tuned by subtle ligand modifications [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

A Pyrazolate Osmium(VI) Nitride Exhibits Anticancer Activity through Modulating Protein Homeostasis in HepG2 Cells

Huang

et al. 2022

IJMS

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Interest in the third-row transition metal osmium and its compounds as potential anticancer agents has grown in recent years. Here, we synthesized the osmium(VI) nitrido complex Na[OsVI(N)(tpm)2] (tpm = [5-(Thien-2-yl)-1H-pyrazol-3-yl]methanol), which exhibited a greater inhibitory effect on the cell viabilities of the cervical, ovarian, and breast cancer cell lines compared with cisplatin. Proteomics analysis revealed that Na[OsVI(N)(tpm)2] modulates the expression of protein-transportation-associated, DNA-metabolism-associated, and oxidative-stress-associated proteins in HepG2 cells. Perturbation of protein expression activity by the complex in cancer cells affects the functions of the mitochondria, resulting in high levels of cellular oxidative stress and low rates of cell survival. Moreover, it caused G2/M phase cell cycle arrest and caspase-mediated apoptosis of HepG2 cells. This study reveals a new high-valent osmium complex as an anticancer agent candidate modulating protein homeostasis.

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Osmium(vi) nitride triggers mitochondria-induced oncosis and apoptosis

Abstract: We report a new osmium(VI) nitrido complex bearing a nonplanar tetradentate ligand with potent anticancer activity. It causes mitochondrial damage, which induces liver cancer cell death via oncosis and apoptosis....

Cited by 7 publications

References 42 publications

Potent anticancer activity of a novel iridium metallodrug via oncosis

Potent anticancer activity of a novel iridium metallodrug via oncosis

Cytotoxic cis-ruthenium(iii) bis(amidine) complexes

A Pyrazolate Osmium(VI) Nitride Exhibits Anticancer Activity through Modulating Protein Homeostasis in HepG2 Cells

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