Rational design of an ESIPT-based fluorescent probe for selectively monitoring glutathione in live cells and zebrafish

Zheng, Yayuan; Zhang, Han-Chen; Tian, Di-Hua; Duan, De-Chen; Dai, Fang; Zhou, Bo

doi:10.1016/j.saa.2020.118429

Cited by 24 publications

(7 citation statements)

References 53 publications

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“…In sharp contrast, the treatment with MitoCur-1 only had a marginal effect on the ROS levels in L02 cells (Figure B,F). Using our recently developed GSH probe BTFMD, we also observed that treatment with MitoCur-1 preferentially induced the decrease of the green fluorescence signal (depletion of intracellular GSH) in HepG2 cells (Figure C,G) over L02 cells (Figure D,H), while pretreatment with DTT markedly reversed the decrease (Figure C,G). We reasoned that the collapse of intracellular redox balance (including the ROS generation and the GSH depletion) in HepG2 cells by MitoCur-1 should stem from the mitochondrial ROS leakage.…”

Section: Resultsmentioning

confidence: 67%

Redox-Based Strategy for Selectively Inducing Energy Crisis Inside Cancer Cells: An Example of Modifying Dietary Curcumin to Target Mitochondria

Zheng

Cui

et al. 2022

J. Agric. Food Chem.

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Reprograming of energy metabolism is a major hallmark of cancer, but its effective intervention is still a challenging task due to metabolic heterogeneity and plasticity of cancer cells. Herein, we report a general redox-based strategy for meeting the challenge. The strategy was exemplified by a dietary curcumin analogue (MitoCur-1) that was designed to target mitochondria (MitoCur-1). By virtue of its electrophilic and mitochondrial-targeting properties, MitoCur-1 generated reactive oxygen species (ROS) more effectively and selectively in HepG2 cells than in L02 cells via the inhibition of mitochondrial antioxidative thioredoxin reductase 2 (TrxR2). The ROS generation preferentially mediated the energy crisis of HepG2 cells in a dual-inhibition fashion against both mitochondrial and glycolytic metabolisms, which could hit the metabolic plasticity of HepG2 cells. The ROS-dependent energy crisis also allowed its preferential killing of HepG2 cells (IC50 = 1.4 μM) over L02 cells (IC50 = 9.1 μM), via induction of cell-cycle arrest, apoptosis and autophagic death, and its high antitumor efficacy in vivo, in nude mice bearing HepG2 tumors (15 mg/kg). These results highlight that inhibiting mitochondrial TrxR2 to produce ROS by electrophiles is a promising redox-based strategy for the effective intervention of cancer cell energy metabolic reprograming.

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Section: Resultsmentioning

confidence: 67%

Redox-Based Strategy for Selectively Inducing Energy Crisis Inside Cancer Cells: An Example of Modifying Dietary Curcumin to Target Mitochondria

Zheng

Cui

et al. 2022

J. Agric. Food Chem.

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“…204 Using 2-(2′-Hydroxyphenyl) benzothiazole (HBT) as the fluorophore, another GSH sensitive probe designated BTFMD (Probe 19) was developed. 205 2,4-Dinitrobenzenesulfonate moiety was chosen as the reactive site, which could be rapidly cleaved to generate BTFM−OH in the presence of GSH, Cys, and homocysteine. An aldehyde substituent was modified onto the probe to decrease the interferences from Cys and homocysteine.…”

Section: Therapeutic Monitoring and Interventions 4211 Gsh/gpx4mentioning

confidence: 99%

Ferroptosis-Based Therapeutic Strategies toward Precision Medicine for Cancer

Shi,

Chen,

2024

J. Med. Chem.

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Ferroptosis is a type of iron-dependent programmed cell death characterized by the dysregulation of iron metabolism and the accumulation of lipid peroxides. This nonapoptotic mode of cell death is implicated in various physiological and pathological processes. Recent findings have underscored its potential as an innovative strategy for cancer treatment, particularly against recalcitrant malignancies that are resistant to conventional therapies. This article focuses on ferroptosis-based therapeutic strategies for precision cancer treatment, covering the molecular mechanisms of ferroptosis, four major types of ferroptosis inducers and their inhibitory effects on diverse carcinomas, the detection of ferroptosis by fluorescent probes, and their implementation in image-guided therapy. These state-of-the-art tactics have manifested enhanced selectivity and efficacy against malignant carcinomas. Given that the administration of ferroptosis in cancer therapy is still at a burgeoning stage, some major challenges and future perspectives are discussed for the clinical translation of ferroptosis into precision cancer treatment. ■ SIGNIFICANCE • The potential of ferroptosis as an innovative strategy for precision cancer therapy is highlighted. • Recent advances are discussed from three perspectives: molecular mechanism and regulation, anti-cancer ferroptosis inducers, and ferroptosis probes for image-guided therapy. • The strengths and weaknesses of ferroptosis modulators and probes are analyzed in terms of current progress and technical barriers. • Future perspectives are emphasized to advance ferroptosis-based therapies toward clinical use for cancer treatment.

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“…Zhou (Zheng et al, 2020). Briefly, the DCFH-DA probe and GSH probe were added to the cells and incubated for 1 h following the instruction; then washed with PBS and the images captured with a fluorescent microscope.…”

Section: Ros and Gsh Measurementmentioning

confidence: 99%

MitoCur‐1 induces ferroptosis to reverse vemurafenib resistance in melanoma through inhibition of USP14

Li,

Zhou,

Wang

et al. 2023

Pigment Cell Melanoma Res

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Melanoma is an aggressive malignant tumor with a poor prognosis. Vemurafenib (PLX4032, vem) is applied to specifically treat BRAF V600E‐mutated melanoma patients. However, prolonged usage of vem makes patients resistant to the drug and finally leads to clinical failure. We previously tested the combination regimen of tubulin inhibitor VERU‐111 with vem, as well as USP14 selective inhibitor b‐AP15 in combination with vem, both of which have showed profound therapeutic effects in overcoming vem resistance in vitro and in vivo. Most importantly, we discovered that vem‐resistant melanoma cell lines highly expressed E3 ligase SKP2 and DUB enzyme USP14, and we have demonstrated that USP14 directly interacts and stabilizes SKP2, which contributes to vem resistance. These works give us a clue that USP14 might be a promising target to overcome vem resistance in melanoma. MitoCur‐1 is a curcumin derivative, which was originally designed to specifically target tumor mitochondria inducing redox imbalance, thereby promoting tumor cell death. In this study, we have demonstrated that it can work as a novel USP14 inhibitor, and thus bears great potential in providing an anti‐tumor effect and sensitizing vem‐resistant cells by inducing ferroptosis in melanoma. Application of MitoCur‐1 dramatically induces USP14 inhibition and inactivation of GPX4 enzyme, meanwhile, increases the depletion of GSH and decreases SLC7A11 expression level. As a result, ferrous iron‐dependent lipid ROS accumulated in the cell, inducing ferroptosis, thus sensitizes the vem‐resistant melanoma cell. Interestingly, overexpression of USP14 antagonized all the ferroptosis cascade events induced by MitoCur‐1, therefore, we conclude that MitoCur‐1 induces ferroptosis through inhibition of USP14. We believe that by inhibition of USP14, vem resistance can be reversed and will finally benefit melanoma patients in future.

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Rational design of an ESIPT-based fluorescent probe for selectively monitoring glutathione in live cells and zebrafish

Cited by 24 publications

References 53 publications

Redox-Based Strategy for Selectively Inducing Energy Crisis Inside Cancer Cells: An Example of Modifying Dietary Curcumin to Target Mitochondria

Redox-Based Strategy for Selectively Inducing Energy Crisis Inside Cancer Cells: An Example of Modifying Dietary Curcumin to Target Mitochondria

Ferroptosis-Based Therapeutic Strategies toward Precision Medicine for Cancer

MitoCur‐1 induces ferroptosis to reverse vemurafenib resistance in melanoma through inhibition of USP14

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