The dissociation of the Hsp60/pro-Caspase-3 complex by bis(pyridyl)oxadiazole copper complex ( CubipyOXA ) leads to cell death in NCI-H292 cancer cells

Bavisotto, Celeste Caruso; Nikolić, Dragana; Gammazza, Antonella Marino; Barone, Rosario; Cascio, Filippa Lo; Mocciaro, Emanuele; Zummo, Giovanni; Macario, Everly Conway de; Macario, Alberto J. L.; Cappello, Francesco; Giacalone, Valentina; Pace, Andrea; Barone, Giampaolo; Piccionello, Antonio Palumbo; Campanella, Claudia

doi:10.1016/j.jinorgbio.2017.02.004

Cited by 38 publications

(32 citation statements)

References 55 publications

(82 reference statements)

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“…They have been considered to be candidates for cancer therapies. Thus, accumulation of HSP60 in tumor cells has been reported, leading to resistance against cell death [51, 58]. On the other hand, it was demonstrated that accumulated HSP60 in the cytosol due to mitochondrial release in stressed cells activates pro-caspase-3, and hence induces apoptosis [59].…”

Section: Discussionmentioning

confidence: 99%

Elevated sodium leads to the increased expression of HSP60 and induces apoptosis in HUVECs

et al. 2017

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Atherosclerosis is the leading cause of death in the world. We have previously shown that expression of heat shock protein 60 (HSP60) on the surface of endothelial cells is the main cause of initiating the disease as it acts as a T cell auto-antigen and can be triggered by classical atherosclerosis risk factors, such as infection (e.g. Chlamydia pneumoniae), chemical stress (smoking, oxygen radicals, drugs), physical insult (heat, shear blood flow) and inflammation (inflammatory cytokines, lipopolysaccharide, oxidized low density lipoprotein, advanced glycation end products). In the present study, we show that increasing levels of sodium chloride can also induce an increase in intracellular and surface expression of HSP60 protein in human umbilical vein endothelial cells. In addition, we found that elevated sodium induces apoptosis.

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Section: Discussionmentioning

confidence: 99%

Elevated sodium leads to the increased expression of HSP60 and induces apoptosis in HUVECs

et al. 2017

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“…In addition, we found that the antitumor agent doxorubicin acted on the NCI-H292 cell line by lowering the levels of intracellular HSP60 and determining the HSP60 acetylation, which seems to be responsible for the disruption of Hsp60/p53 complex and the activation of replicative senescence, probably via p53-p21 pathway [51]. Our previous findings reported that high levels of HSP60 may have an anti-apoptotic and cytoprotective role in cancer [15,[50][51][52]. Compounds that cause the reduction of HSP60 levels may have various effects, as has already been demonstrated.…”

Section: Discussionmentioning

confidence: 86%

“…In a mucoepidermoid carcinoma cell line (NCI-H292), we demonstrated that the high levels of HSP60 caused the inhibition of the pro-caspase 3 (pC3) activation and the resistance to apoptosis. The treatment with a copper compound with cytotoxic properties induced the decrease in the HSP60 levels, the separation of the complex HSP60/pC3, and consequently, the C3 activation of the caspase pathway associated with a tumor-cell growth arrest [50]. In addition, we found that the antitumor agent doxorubicin acted on the NCI-H292 cell line by lowering the levels of intracellular HSP60 and determining the HSP60 acetylation, which seems to be responsible for the disruption of Hsp60/p53 complex and the activation of replicative senescence, probably via p53-p21 pathway [51].…”

Section: Discussionmentioning

confidence: 99%

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Curcumin Affects HSP60 Folding Activity and Levels in Neuroblastoma Cells

Bavisotto

Gammazza

Cascio

et al. 2020

IJMS

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The fundamental challenge in fighting cancer is the development of protective agents able to interfere with the classical pathways of malignant transformation, such as extracellular matrix remodeling, epithelial–mesenchymal transition and, alteration of protein homeostasis. In the tumors of the brain, proteotoxic stress represents one of the main triggering agents for cell transformation. Curcumin is a natural compound with anti-inflammatory and anti-cancer properties with promising potential for the development of therapeutic drugs for the treatment of cancer as well as neurodegenerative diseases. Among the mediators of cancer development, HSP60 is a key factor for the maintenance of protein homeostasis and cell survival. High HSP60 levels were correlated, in particular, with cancer development and progression, and for this reason, we investigated the ability of curcumin to affect HSP60 expression, localization, and post-translational modifications using a neuroblastoma cell line. We have also looked at the ability of curcumin to interfere with the HSP60/HSP10 folding machinery. The cells were treated with 6, 12.5, and 25 µM of curcumin for 24 h, and the flow cytometry analysis showed that the compound induced apoptosis in a dose-dependent manner with a higher percentage of apoptotic cells at 25 µM. This dose of curcumin-induced a decrease in HSP60 protein levels and an upregulation of HSP60 mRNA expression. Moreover, 25 µM of curcumin reduced HSP60 ubiquitination and nitration, and the chaperonin levels were higher in the culture media compared with the untreated cells. Furthermore, curcumin at the same dose was able to favor HSP60 folding activity. The reduction of HSP60 levels, together with the increase in its folding activity and the secretion in the media led to the supposition that curcumin might interfere with cancer progression with a protective mechanism involving the chaperonin.

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“…In the COPD-BS group, no differences were found in the severity stratification. Hsp60 is a pro-inflammatory protein that promotes the production of IL-1b, IL-6, and TNF-a, as well as tumoral-cell survival and nitrogen oxidative species (NOS) production (Caruso Bavisotto et al, 2017;Sangiorgi et al, 2017). At the pulmonary level, Hsp60 is described as an extracellular-stimulation signal for inflammatory activity; Hsp60 is released by epithelial cells when it reaches high levels in response to oxidative stress (Cappello et al, 2006;Sangiorgi et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Effect of SNPs in HSP Family Genes, Variation in the mRNA and Intracellular Hsp Levels in COPD Secondary to Tobacco Smoking and Biomass-Burning Smoke

et al. 2020

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Heat shock proteins (HSP) genes are a superfamily responsible for encoding highly conserved proteins that are important for antigen presentation, immune response regulation, and cellular housekeeping processes. These proteins can be increased by cellular stress related to pollution, for example, smoke from biomass burning and/or tobacco smoking. Single nucleotide polymorphisms (SNPs) in these genes could affect the levels of their proteins, as well as the susceptibility to developing lung diseases, such as chronic obstructive pulmonary disease (COPD), related to the exposure to environmental factors.Methods: The subjects included were organized into two comparison groups: 1,103 smokers (COPD patients, COPD-S = 360; smokers without COPD, SWOC = 743) and 442 never-smokers who were chronically exposed to biomass smoke (COPD patients, COPD-BS = 244; exposed without COPD, BBES = 198). Eight SNPs in three HSP genes were selected and genotyped: four in HSPA1A, two in HSPA1B, and two in HSPA1L. Sputum expectoration was induced to obtain pulmonary cells and relative quantification of mRNA expression. Subsequently, the intracellular protein levels of total Hsp27, phosphorylated Hsp27 (Hsp27p), Hsp60, and Hsp70 were measured in a sample of 148 individuals selected based on genotypes.

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The dissociation of the Hsp60/pro-Caspase-3 complex by bis(pyridyl)oxadiazole copper complex ( CubipyOXA ) leads to cell death in NCI-H292 cancer cells

Cited by 38 publications

References 55 publications

Elevated sodium leads to the increased expression of HSP60 and induces apoptosis in HUVECs

Elevated sodium leads to the increased expression of HSP60 and induces apoptosis in HUVECs

Curcumin Affects HSP60 Folding Activity and Levels in Neuroblastoma Cells

Effect of SNPs in HSP Family Genes, Variation in the mRNA and Intracellular Hsp Levels in COPD Secondary to Tobacco Smoking and Biomass-Burning Smoke

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