Modulatory effects of curcumin on heat shock proteins in cancer: A promising therapeutic approach

Forouzanfar, Fatemeh; Barreto, George E.; Majeed, Muhammed; Sahebkar, Amirhossein

doi:10.1002/biof.1522

Cited by 22 publications

(13 citation statements)

References 107 publications

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“…Curcumin and several natural derived-products have been shown to regulate many members of HSPs. These compounds show a significant inhibitory activity of HSP60-induced cell proliferation [21,22]. Therefore, these data encourage the idea that the polyphenolic structure of curcumin might be a recognition motif for HSP60 s binding [22].…”

Section: Introductionsupporting

confidence: 61%

“…These compounds show a significant inhibitory activity of HSP60-induced cell proliferation [21,22]. Therefore, these data encourage the idea that the polyphenolic structure of curcumin might be a recognition motif for HSP60 s binding [22]. Here, we reported the study of the effects of curcumin on HSP60 levels, PTMs, and folding activity using a neuroblastoma cell line.…”

Section: Introductionmentioning

confidence: 58%

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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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Section: Introductionsupporting

confidence: 61%

Section: Introductionmentioning

confidence: 58%

Curcumin Affects HSP60 Folding Activity and Levels in Neuroblastoma Cells

Bavisotto

Gammazza

Cascio

et al. 2020

IJMS

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“…Hsp60 activated TREM2-associated signaling pathway and enhanced microglial phagocytosis via binding to the immunoglobulin region of TREM2 ectodomain. Although the underlying biochemical pathway mediated by Hsp60 is still unclear, it has been widely accepted as a potential target for other diseases including atherosclerosis and cancer [ 122 – 124 ]. Hence, the pharmaceutical experiences of Hsp60 applied in other diseases should be referred to explore the potential strategies to treat AD.…”

Section: (S)trem2 As Therapeutic Targetsmentioning

confidence: 99%

TREM2 ectodomain and its soluble form in Alzheimer’s disease

Yang

Zhang

et al. 2020

J Neuroinflammation

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Triggering receptor expressed on myeloid cells 2 (TREM2) is a receptor mainly expressed on the surface of microglia. It mediates multiple pathophysiological processes in various diseases. Recently, TREM2 has been found to play a role in the development of Alzheimer's disease (AD). TREM2 is a transmembrane protein that is specifically expressed on microglia in the brain. It contains a long ectodomain that directly interacts with the extracellular environment to regulate microglial function. The ectodomain of TREM2 is processed by a disintegrin and metalloprotease, resulting in the release of a soluble form of TREM2 (sTREM2). Recent studies have demonstrated that sTREM2 is a bioactive molecule capable of binding ligands, activating microglia, and regulating immune responses during the AD continuum. Clinical studies revealed that sTREM2 level is elevated in cerebrospinal fluid (CSF) of AD patients, and the sTREM2 level is positively correlated with the levels of classical CSF biomarkers, namely t-tau and p-tau, indicating that it is a reliable predictor of the early stages of AD. Herein, we summarize the key results on the generation, structure, and function of sTREM2 to provide new insights into TREM2-related mechanisms underlying AD pathogenesis and to promote the development of TREM2-based therapeutic strategy.

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“…Such research reveals that common Indian herbs and spices such as turmeric, garlic, ginger, black pepper, coriander and others, contain phytochemicals that display a range of neuroprotective properties ( Kannappan et al, 2011 ). They have been shown to be antioxidant, anti-inflammatory, anti-amyloidogenic and also to upregulate protective cellular responses like heat shock responses ( Forouzanfar et al, 2019 ). As misfolding and aggregation of tau and amyloid proteins, oxidative stress and aberrant inflammation are all implicated in AD, it is not surprising that these spice-derived nutraceuticals have shown some disease-modifying potential in AD models.…”

Section: Introductionmentioning

confidence: 99%

Curcumin as a Holistic Treatment for Tau Pathology

Sivanantharajah

Mudher

2022

Front. Pharmacol.

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Global forecasts for prevalence of Alzheimer’s Disease (AD) estimate that 152.8 million people will have dementia in 2050, a sharp rise from 57.4 million in 2019 (GBD 2019). This rise can be attributable to increases in population growth and aging, but in the absence of disease-modifying therapies it poses a huge societal challenge that must be addressed urgently. One way to combat this challenge is to explore the utility of holistic treatments that may protect against AD, including traditional herbs, spices and other nutraceuticals that are pharmacologically safe, inexpensive and readily available. In this light, the spice turmeric, and its active ingredient curcumin, has been investigated as a potential holistic treatment for AD over the past 2 decades; however, promising results with animal studies have not translated to success in clinical trials. One issue is that most animal models examining the effects of curcumin and curcumin derivatives in AD have been done with a focus at ameliorating amyloid pathology. Due to the limited success of Amyloid-β-based drugs in recent clinical trials, tau-focused therapeutics provide a promising alternative. In this article, we aim to provide a clearer picture of what is currently known about the effectiveness of curcumin and curcumin derivatives to ameliorate tau pathology. Tau focused studies may help inform more successful clinical studies by placing greater emphasis on the development and optimised delivery of curcumin derivatives that more effectively target tau pathology.

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Modulatory effects of curcumin on heat shock proteins in cancer: A promising therapeutic approach

Cited by 22 publications

References 107 publications

Curcumin Affects HSP60 Folding Activity and Levels in Neuroblastoma Cells

Curcumin Affects HSP60 Folding Activity and Levels in Neuroblastoma Cells

TREM2 ectodomain and its soluble form in Alzheimer’s disease

Curcumin as a Holistic Treatment for Tau Pathology

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