Impairment of the autophagy-related lysosomal degradation pathway by an anticancer rhenium(<scp>i</scp>) complex

He, Liangmei; Zhang, Pan; Qin, Weiwei; Li, Yang; Tan, Cai‐Ping; Mao, Zong‐Wan

doi:10.1039/c9dt00322c

Cited by 64 publications

(58 citation statements)

References 43 publications

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“…6b', b'', d' and d''). Such cytosolic-lysosomal distribution of the rhenium(I) trycarbonyl complexes has previously been reported in molecules bearing β-carboline, 68 1,10-phenanthroline 49,104 and diimine ligands. 57 Preferential accumulation in lysosomes, mitochondria or localization only in cytoplasm has also been evidenced for other rhenium(I) tricarbonyl molecules.…”

Section: Inhibition Of Angiogenesissupporting

confidence: 74%

“…The anticancer activity of fac-[Re(CO)3] + compounds has been tested on several different cancer cell lines. The majority of the studies were focused on antiproliferative effects on cervical, 30-33, 47, 51, 57-61 ovarian, 62,63 breast, 12,20,25,[64][65][66] and epithelial adenocarcinoma 24,49,67,68 cell lines showing IC50 values as low as e.g. 0.1 (HeLa), 30 1 (MCF-7), 15 0.75 (A549), 67 4 (NB69 and H4 cells) μM.…”

Section: In Vitro Anticancer Activity Evaluationmentioning

confidence: 99%

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Highly Potent Rhenium(I) Tricarbonyl Complexes with Dual Anticancer and Anti-Angiogenic Activity Against Colorectal Carcinoma

Delasoie¹,

Pavić²,

Voutier³

et al. 2020

Preprint

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Synthesized and characterized a series of rhenium(I) trycarbonyl-based complexes with increased lipophilicity. Two of these novel compounds were discovered to possess remarkable anticancer, anti-angiogenic and antimetastatic activity <i>in vivo</i> (zebrafish-human CRC xenograft model), being effective at very low doses (1-3 µM). At doses as high as 250 µM the complexes did not provoke toxicity issues encountered in clinical anticancer drugs (cardio-, hepato-, and myelotoxicity). The two compounds exceed the antiproliferative and anti-angiogenic potency of clinical drugs cisplatin and sunitinib-malate, and display a large therapeutic window.

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Section: Inhibition Of Angiogenesissupporting

confidence: 74%

Section: In Vitro Anticancer Activity Evaluationmentioning

confidence: 99%

Highly Potent Rhenium(I) Tricarbonyl Complexes with Dual Anticancer and Anti-Angiogenic Activity Against Colorectal Carcinoma

Delasoie¹,

Pavić²,

Voutier³

et al. 2020

Preprint

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“…It has been shown that both FGFR1 and Src can be inactivated by a mechanism involving the direct oxidation of a speci c cysteine residue (Cys-277 in Src and Cys-488 in FGFR1) (37). Furthermore, it has been suggested that tricarbonyl rhenium complexes exert anticancer activity by elevating intracellular levels of reactive oxygen species (ROS) (17). Therefore, we determined the ability of JVG045 to induce the production of intracellular ROS.…”

Section: Resultsmentioning

confidence: 99%

“…To test the effect of JVG045 on pancreatic cancer cells with varying degrees of genetic complexity (ATCC ® TCP-1026), we exposed a range of cell lines to JVG045. These experiments showed that, compared to K-RAS mutated cell lines (IC50 AsPC1 4.0±1.2mM, HPAF-II 5.6±0.6mM, CFPAC 5.7±2.8mM (25) and Supplementary Table 2), JVG045 had an insigni cant effect on the only cell line that contains wild-type RAS and is not RAS-activated, BxPC-3 (IC50 >20mM; One-way ANOVA, F (5,17) =0.6535, p=0.6630; Fig 5A). In contrast, SW1990, a pancreatic cancer cell line with mutationally activated KRAS but bearing wild type tumour suppressor P53, displayed a statistically signi cant dose-dependent reduction of cell number in response to JVG045 treatment (IC50 = 5.4mM; One-way ANOVA, F (5,12) =8.208, p=0.0014; Fig 5A).…”

Section: Re-nhc Complexes Show Anticancer Activity In Neuroblastoma Cmentioning

confidence: 98%

Rhenium N-heterocyclic Carbene Complexes Block Growth of Aggressive Cancers by Inhibiting FGFR- and SRC-Mediated Signalling

Domenichini

Casari

Simpson

et al. 2020

Preprint

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Background: Platinum-based anticancer drugs have been at the frontline of cancer therapy for the last 40 years, and are used in more than half of all treatments for different cancer types. However, they are not universally effective, and patients often suffer severe side effects because of their lack of cellular selectivity. There is therefore a compelling need to investigate the anticancer activity of alternative metal complexes. Here we describe the potential anticancer activity of rhenium-based complexes with preclinical efficacy in different types of solid malignancies.Methods: Kinase profile assay of rhenium complexes. Toxicology studies using zebrafish. Analysis of the growth of pancreatic cancer cell line-derived xenografts generated in zebrafish and in mice upon exposure to rhenium compounds.Results: We describe rhenium complexes which block cancer proliferation in vitro by inhibiting the signalling cascade induced by FGFR and Src. Initially, we tested the toxicity of rhenium complexes in vivo using a zebrafish model and identified one compound that displays anticancer activity with low toxicity even in the high micromolar range. Notably, the rhenium complex has anticancer activity in very aggressive cancers such as pancreatic ductal adenocarcinoma and neuroblastoma. We demonstrate the potential efficacy of this complex via a significant reduction in cancer growth in mouse xenografts.Conclusions: Our findings provide a basis for the development of rhenium-based chemotherapy agents with enhanced selectivity and limited side effects compared to standard platinum-based drugs.

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“…Then, they proceeded with in vivo testing of the most cytotoxic complex, complex 15a on mice which were transplanted with A549 cancer cells. It is reported that a 5 mg/kg dose of complex 15a is required to cause lysosomal dysfunction and cell death through autophagy over a three-week treatment [ 119 ]. The coordination of pyridine and β-carboline ligands did enhanced the anticancer activity of the Re(I) complex.…”

Section: Re(i) Tricarbonyl Complexes: In Vivo Studiesmentioning

confidence: 99%

Recent Emergence of Rhenium(I) Tricarbonyl Complexes as Photosensitisers for Cancer Therapy

Liew

Zulkefeli

et al. 2020

Molecules

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Photodynamic therapy (PDT) is emerging as a significant complementary or alternative approach for cancer treatment. PDT drugs act as photosensitisers, which upon using appropriate wavelength light and in the presence of molecular oxygen, can lead to cell death. Herein, we reviewed the general characteristics of the different generation of photosensitisers. We also outlined the emergence of rhenium (Re) and more specifically, Re(I) tricarbonyl complexes as a new generation of metal-based photosensitisers for photodynamic therapy that are of great interest in multidisciplinary research. The photophysical properties and structures of Re(I) complexes discussed in this review are summarised to determine basic features and similarities among the structures that are important for their phototoxic activity and future investigations. We further examined the in vitro and in vivo efficacies of the Re(I) complexes that have been synthesised for anticancer purposes. We also discussed Re(I) complexes in conjunction with the advancement of two-photon PDT, drug combination study, nanomedicine, and photothermal therapy to overcome the limitation of such complexes, which generally absorb short wavelengths.

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Impairment of the autophagy-related lysosomal degradation pathway by an anticancer rhenium(i) complex

Abstract: A Re(i) complex induces autophagy, which is arrested at the lysosomal stage due to lysosomal dysfunction, and inhibits tumor growth in vivo.

Cited by 64 publications

References 43 publications

Highly Potent Rhenium(I) Tricarbonyl Complexes with Dual Anticancer and Anti-Angiogenic Activity Against Colorectal Carcinoma

Highly Potent Rhenium(I) Tricarbonyl Complexes with Dual Anticancer and Anti-Angiogenic Activity Against Colorectal Carcinoma

Rhenium N-heterocyclic Carbene Complexes Block Growth of Aggressive Cancers by Inhibiting FGFR- and SRC-Mediated Signalling

Recent Emergence of Rhenium(I) Tricarbonyl Complexes as Photosensitisers for Cancer Therapy

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