Endoplasmic reticulum stress: an arising target for metal-based anticancer agents

King, Anna; Wilson, Justin J.

doi:10.1039/d0cs00259c

Cited by 144 publications

(118 citation statements)

References 191 publications

Supporting

Mentioning

115

Contrasting

Unclassified

Order By: Relevance

“…Ca 2+ overload also plays an important role in the occurrence of drug-induced ERS (Cheng et al, 2018). Drugs initiate the Ca 2+ channels on the tumor cell membrane after entering the cell through the transporters, which causes the influx of extracellular Ca 2+ (King and Wilson, 2020). Ca 2+ is released from the ER when the Ca 2+ concentration in the cytoplasm reaches a certain level (Cai et al, 2016), which can lead to Ca 2+ overload (Nyberg and Espinosa, 2016).…”

Section: Drug-induced Ers In Solid Tumorsmentioning

confidence: 99%

The Road of Solid Tumor Survival: From Drug-Induced Endoplasmic Reticulum Stress to Drug Resistance

Cao

Tang

Huang

et al. 2021

Front. Mol. Biosci.

View full text Add to dashboard Cite

Endoplasmic reticulum stress (ERS), which refers to a series of adaptive responses to the disruption of endoplasmic reticulum (ER) homeostasis, occurs when cells are treated by drugs or undergo microenvironmental changes that cause the accumulation of unfolded/misfolded proteins. ERS is one of the key responses during the drug treatment of solid tumors. Drugs induce ERS by reactive oxygen species (ROS) accumulation and Ca2+ overload. The unfolded protein response (UPR) is one of ERS. Studies have indicated that the mechanism of ERS-mediated drug resistance is primarily associated with UPR, which has three main sensors (PERK, IRE1α, and ATF6). ERS-mediated drug resistance in solid tumor cells is both intrinsic and extrinsic. Intrinsic ERS in the solid tumor cells, the signal pathway of UPR-mediated drug resistance, includes apoptosis inhibition signal pathway, protective autophagy signal pathway, ABC transporter signal pathway, Wnt/β-Catenin signal pathway, and noncoding RNA. Among them, apoptosis inhibition is one of the major causes of drug resistance. Drugs activate ERS and its downstream antiapoptotic proteins, which leads to drug resistance. Protective autophagy promotes the survival of solid tumor cells by devouring the damaged organelles and other materials and providing new energy for the cells. ERS induces protective autophagy by promoting the expression of autophagy-related genes, such as Beclin-1 and ATG5–ATG12. ABC transporters pump drugs out of the cell, which reduces the drug-induced apoptosis effect and leads to drug resistance. In addition, the Wnt/β-catenin signal pathway is also involved in the drug resistance of solid tumor cells. Furthermore, noncoding RNA regulates the ERS-mediated survival and death of solid tumor cells. Extrinsic ERS in the solid tumor cells, such as ERS in immune cells of the tumor microenvironment (TME), also plays a crucial role in drug resistance by triggering immunosuppression. In immune system cells, ERS in dendritic cells (DCs) and myeloid-derived suppressor cells (MDSCs) influences the antitumor function of normal T cells, which results in immunosuppression. Meanwhile, ERS in T cells can also cause impaired functioning and apoptosis, leading to immunosuppression. In this review, we highlight the core molecular mechanism of drug-induced ERS involved in drug resistance, thereby providing a new strategy for solid tumor treatment.

show abstract

Section: Drug-induced Ers In Solid Tumorsmentioning

confidence: 99%

The Road of Solid Tumor Survival: From Drug-Induced Endoplasmic Reticulum Stress to Drug Resistance

Cao

Tang

Huang

et al. 2021

Front. Mol. Biosci.

View full text Add to dashboard Cite

show abstract

“…Capitalizing on these advantages, a variety of metal-containing compounds have already been clinically approved for a wide range of therapeutic applications. Increasing efforts to not only identify bioactive metal complexes [41] but deeply understand their mechanism of action [87][88][89][90] will be an important next step in their advancement and greater acceptance in the medical community (see Outstanding questions). Further investigation into the therapeutic applications of metal complexes will yield novel compounds with increased potency and selectivity and may even lead to the discovery of entirely new therapeutic strategies.…”

Section: Discussionmentioning

confidence: 99%

Metal complexes for therapeutic applications

Karges¹,

Stokes²,

Cohen³

2021

Trends in Chemistry

112

View full text Add to dashboard Cite

“…The Pearson's correlation coefficient of Ir-cR8 with different markers showed that, although diffused in the cell, Ir-cR8 preferred to distribute in the endoplasmic reticulum and the mitochondria rather than in the lysosomes, a localisation potentially having correlation with the oncosis-like cell death. 55 Next, the intracellular molecular mechanisms that may be associated with this mode of death were investigated. As the signalling pathways that regulate oncosis have not been fully elucidated, circumstantial evidence was searched to verify whether the cell death caused by the Ir-peptides was of oncotic nature.…”

Section: Resultsmentioning

confidence: 99%

Structure-tuned membrane active Ir-complexed oligoarginine overcomes cancer cell drug resistance and triggers immune responses in mice

Yang

Chen

et al. 2020

Chem. Sci.

View full text Add to dashboard Cite

show abstract

Endoplasmic reticulum stress: an arising target for metal-based anticancer agents

Abstract: Metal anticancer agents are rapidly emerging as selective, potent therapeutics that exhibit anticancer activity by inducing endoplasmic reticulum stress.

Cited by 144 publications

References 191 publications

The Road of Solid Tumor Survival: From Drug-Induced Endoplasmic Reticulum Stress to Drug Resistance

The Road of Solid Tumor Survival: From Drug-Induced Endoplasmic Reticulum Stress to Drug Resistance

Metal complexes for therapeutic applications

Structure-tuned membrane active Ir-complexed oligoarginine overcomes cancer cell drug resistance and triggers immune responses in mice

Contact Info

Product

Resources

About