Current Understanding of HSP90 as a Novel Therapeutic Target: An Emerging Approach for the Treatment of Cancer

Haque, Absarul; Alam, Qamre; Alam, Mohammad Zubair; Azhar, Esam I.; Sait, Khalid; Anfinan, Nisrin; Mushtaq, Gohar; Kamal, Mohammad Amjad; Rasool, Mahmood

doi:10.2174/1381612822666160325152200

Cited by 37 publications

(34 citation statements)

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“…HSP90 is normally required for protein stabilization essential to tumour progress [16]. Therefore, the protein is always considered as a drug target for cancer therapy and research [17]. However, the function of HSP90 involved in neural damage and cellular oxidative stress is rarely reported wildly.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of HSP90 Promotes Neural Stem Cell Survival from Oxidative Stress through Attenuating NF‐κB/p65 Activation

Liu

Jiang

et al. 2016

Oxidative Medicine and Cellular Longevity

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Stem cell survival after transplantation determines the efficiency of stem cell treatment, which develops as a novel potential therapy for several central nervous system (CNS) diseases in recent decades. The engrafted stem cells face the damage of oxidative stress, inflammation, and immune response at the lesion point in host. Among the damaging pathologies, oxidative stress directs stem cells to apoptosis and even death through several signalling pathways and DNA damage. However, the in-detail mechanism of stem cell survival from oxidative stress has not been revealed clearly. Here, in this study, we used hydrogen peroxide (H2O2) to induce the oxidative damage on neural stem cells (NSCs). The damage was in consequence demonstrated involving the activation of heat shock protein 90 (HSP90) and NF-κB/p65 signalling pathways. Further application of the pharmacological inhibitors, respectively, targeting at each signalling indicated an upper-stream role of HSP90 upon NF-κB/p65 on NSCs survival. Preinhibition of HSP90 with the specific inhibitor displayed a significant protection on NSCs against oxidative stress. In conclusion, inhibition of HSP90 would attenuate NF-κB/p65 activation by oxidative induction and promote NSCs survival from oxidative damage. The HSP90/NF-κB mechanism provides a new evidence on rescuing NSCs from oxidative stress and also promotes the stem cell application on CNS pathologies.

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Section: Discussionmentioning

confidence: 99%

Inhibition of HSP90 Promotes Neural Stem Cell Survival from Oxidative Stress through Attenuating NF‐κB/p65 Activation

Liu

Jiang

et al. 2016

Oxidative Medicine and Cellular Longevity

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“…Heat shock proteins (HSPs) are stress-responsive family of proteins, which are involved in posttranslational modifications, protein folding, and aggregation and disaggregation of proteins. Heat shock protein 90 (HSP90) is a ubiquitous molecular chaperone involved in conformational stabilization, maturation and activity of its client proteins [ 32 ]. In addition, HSP90 assists the degradation of oxidized proteins and thereby prevents oxidative stress in cells [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Protein Profile in Mice with Low or Excessive Selenium Diets

Wang

Zhang

et al. 2016

IJMS

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Dietary selenium putatively prevents oxidative damage, whereas excessive selenium may lead to animal disorder. In this study, we investigated the effects of low and excessive levels of dietary selenium on oxidative stress and mitochondrial proteins in mouse liver. Six to eight week old mice were fed a diet with low, excessive, or moderate (control) levels of selenium (sodium selenite). The selenium concentration and oxidative stress-related parameters in hepatic mitochondria were evaluated. Two-dimensional electrophoresis and mass spectrometry were applied to identify the differentially-expressed proteins associated with dietary selenium. The selenium content of the livers in mice with the low selenium diet was significantly lower than that of the control, while that of mice fed excessive levels was significantly higher. In both groups oxidative stress in hepatic mitochondria was found; accompanied by lower superoxide dismutase (SOD) and glutathione peroxidase (GPX) levels and higher malondialdehyde (MDA) content, compared with the control group. Furthermore, ten proteins in the hepatic mitochondria of the selenium-low or -excessive groups with more than two-fold differences in abundance compared with the control group were identified. The differentially-expressed proteins in hepatic mitochondria may be associated with dietary (low or excessive) selenium-induced oxidative stress.

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“…HSP90 homologs are the major intracellular chaperones that ensure the correct folding and function of proteins by interacting with various intracellular proteins [2,3,17,18]. HSP90 has been implicated in promoting the tumor growth and metastasis of breast cancer, leukemia, pancreatic cancer, and ovarian cancer [19][20][21]. exists in the mitochondria.…”

Section: Hsp90 Familymentioning

confidence: 99%

Roles of Extracellular Vesicles (EVs) Carrying HSPs in Cancer Biomarkers, Immune Surveillance, and Immune Evasion

Taha¹,

Ono²,

Eguchi³

2019

Preprint

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Extracellular vesicles (EV) released by tumor cells are a major aspect of the resistance-associated secretory phenotype (RASP), by which immune evasion can be established. Heat shock proteins (HSPs) are an evolutionarily conserved family of molecular chaperones, which stabilize proteins, minimize protein misfolding and aggregation within the cell, besides facilitating protein translocation, refolding and degradation. (i) Releases of extracellular HSPs (ex-HSP) and EV-associated HSPs (EV-HSP) are essential in RASP, by which molecular cotransfer of HSPs with oncogenic factors into recipient cells can promote cancer progression and resistance against stress such as hypoxia, radiation, chemicals, and immune system. (ii) RASP of tumor cells can eject anticancer drugs, molecularly targeted therapeutics, and immune checkpoint inhibitors with EVs. (iii) Cytotoxic lipids can be also released from tumor cells as RASP. Nevertheless, ex-HSP and EV-HSP can play immunostimulatory and immunosuppressive roles by binding to receptors such as LRP1/CD91/A2MR, scavenger receptors, and toll-like receptors expressed on recipient cells. Liquid biopsy of HSPs in body fluids may be useful in diagnosis, prognosis, and treatment in cancer. Regarding HSP90-targeted therapeutics, we summarize the pros, cons, and problem solutions in this review. Although production of HSPs are canonically induced by heat shock factor 1 (HSF1) and hypoxia-inducible factor 1 (HIF-1), recent studies discovered that production of HSPs is also regulated by matrix metalloproteinase 3 (MMP3) and heterochromatin protein 1 (HP1) and production of cochaperone CDC37 is reciprocally regulated by myeloid zinc finger 1 (MZF1) and SCAN-D1.

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Current Understanding of HSP90 as a Novel Therapeutic Target: An Emerging Approach for the Treatment of Cancer

Cited by 37 publications

References 0 publications

Inhibition of HSP90 Promotes Neural Stem Cell Survival from Oxidative Stress through Attenuating NF‐κB/p65 Activation

Inhibition of HSP90 Promotes Neural Stem Cell Survival from Oxidative Stress through Attenuating NF‐κB/p65 Activation

Mitochondrial Protein Profile in Mice with Low or Excessive Selenium Diets

Roles of Extracellular Vesicles (EVs) Carrying HSPs in Cancer Biomarkers, Immune Surveillance, and Immune Evasion

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