Hyperthermia and protein homeostasis: Cytoprotection and cell death

Ahmed, Kawsar; Zaidi, Syed Faisal; Mati-ur-Rehman,; Rehman, Rafey; Kondo, Takashi

doi:10.1016/j.jtherbio.2020.102615

Cited by 55 publications

(40 citation statements)

References 86 publications

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“…Our experimental data also indicated that hyperthermia could induce autophagy in both hypoxia and normoxic starvation microenvironments, and that autophagy was further enhanced in hypoxia condition. This might stem from the following reasons: HT-induced protein denaturation and aggregation results in the up regulation of HSPs, which are reported to up-regulate the autophagy mediator Beclin-1 [14]. Moreover, Hyperthermia can induce oxidative stress in cells and can further augment the generation of ROS [47].…”

Section: Discussionmentioning

confidence: 99%

“…However, tumor cells possess homeostatic responses to reduce heat-shock induced cell death, which involve cell cycle arrest and transient induction of the transcription of genes encoding molecular chaperones and heat shock proteins (HSPs) [13]. In short, hyperthermia induces the expression of HSPs and inhibit DNA damaged repair, whereas DNA damage, hyperthermia and HPSs evokes autophagy, which was associated with facilitated cell survival and decreased programmed cell death [13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, HSPs and autophagy are two controllers of cellular proteostasis. Under stressful cellular conditions, these two mechanisms are likely to complement each other [14]. However, whether hyperthermia-induced autophagy facilitates cell survival or accelerates cell death during the development of OSCC is still controversial.…”

Section: Introductionmentioning

confidence: 99%

“…Hyperthermia (HT) has been successfully used in the clinical treatment of many cancers including the head and neck cancer [8] for decades, which sensitizes tumor cells to radiation by inhibiting DNA repair and increasing the aggregation of damaged nuclear proteins [9,10]. Previous studies have shown that initiating triggers for death in heat-shocked cells include: induction of physiological cascades; thermal protein unfolding and aggregation; necrosis that occurred at extremely elevated temperatures [14,15]. Furthermore, hyperthermia-related elevated blood ow and vascular permeability in the heated tumor region also promote higher intratumor and peritumor drug concentrations to improve the e cacy of chemotherapy [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

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Hyperthermia combined chemotherapy regulates energy metabolism of cancer cells under hypoxic microenvironment

Shi

Luo

Zhou

et al. 2020

Preprint

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Objective: Oral squamous cell carcinoma (OSCC) represents one of the main types of head and neck malignant tumors with high incidence and mortality as well extremely poor prognosis. Hyperthermia (HT) shows great promises for tumor therapy. However it can promote autophagy in tumor microenvironment, which is found to serve as a surviving mechanism for cancer cells. Inhibiting autophagy has been considered as an adjuvant anti-cancer strategy. The present study investigated the role of HT-induced autophagy, while attempting to combine chemotherapy and autophagy blocking with HT in OSCC cells under hypoxia and starvation microenvironment.Materials and methods: HIF-1α and Beclin-1 expression in tissues was determined by immunohistochemistry in 80 OSCC sample pairs. The IC50 of CoCl2, YC-1 (an inhibitor of HIF-1α) and 3-MA (an inhibitor of autophagy) was detected by CCK-8. CoCl2 and complete culture medium without serum were used to achieve the hypoxic and nutrient deficient microenvironment, respectively. HT was performed by heating in a 42 ℃ water bath. The role of HT and YC-1,3-MA on autophagy in vitro were assessed by qRT-PCR and Western blot, and the secretion of high mobility group box1 (HMGB1) was determined by ELISA. The migration and apoptosis rates of cells were assessed by wound healing assay and flow cytometry.Results: We observed that HIF-1α and Beclin1 were highly expressed in OSCC tissues, which were correlated with more advanced malignancy features. CoCl2 could establish hypoxia microenvironment, induce HIF-1α expression with dose-dependence as well as promote cell migration in Cal-27 and SCC-15 cells. Notably, hyperthermia and hypoxia could activate the HIF-1α/BNIP3/Beclin1 signaling pathway and promote HMGB1 secretion, which triggered cytoprotective autophagy to counteract the hypoxia and starvation cellular stresses, as indicated by downregulation of p62 and light chain 3-II (LC3 II). Furthermore, we found that hyperthermia combined YC-1 and/or 3-MA suppressed autophagy and cell migration whereas facilitated cell apoptosis.Conclusion: The present study demonstrated that combined use of YC-1 and 3-MA might increase death of tumor cells in physiological and hyperthermia conditions, which could be relevant with the inhibition of autophagy in OSCC tumor cells under hypoxia microenvironment in vitro.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Hyperthermia combined chemotherapy regulates energy metabolism of cancer cells under hypoxic microenvironment

Shi

Luo

Zhou

et al. 2020

Preprint

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“…The essential function of these proteins is to serve as molecular chaperones that maintain numerous cellular proteins in their normal three-dimensional structures, in order to continue performing their normal functions when the ambient temperature is increased (1)(2)(3). However, the majority of heat shock proteins also have numerous other functions and are often overexpressed in various situations of cellular stress (1,2,(4)(5)(6)(7). For example, when normal cells evolve into cancer cells, the expression of HSPs is often increased, which is usually a mechanism by which cancer cells become resistant to various therapies (5,7).…”

Section: Introductionmentioning

confidence: 99%

At elevated temperatures, heat shock protein genes show altered ratios of different RNAs and expression of new RNAs, including several novel HSPB1 mRNAs encoding HSP27 protein isoforms

et al. 2021

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Heat shock proteins (HSP) serve as chaperones to maintain the physiological conformation and function of numerous cellular proteins when the ambient temperature is increased. To determine how accurate the general assumption that HSP gene expression is increased in febrile situations is, the RNA levels of the HSF1 (heat shock transcription factor 1) gene and certain HSP genes were determined in three cell lines cultured at 37˚C or 39˚C for three days. At 39˚C, the expression of HSF1, HSPB1, HSP90AA1 and HSP70A1L genes demonstrated complex changes in the ratios of expression levels between different RNA variants of the same gene. Several older versions of the RNAs of certain HSP genes that have been replaced by a newer version in the National Center for Biotechnology Information database were also detected, indicating that the older versions are actually RNA variants of these genes. The present study cloned four new RNA variants of the HSP27-encoding HSPB1 gene, which together encode three short HSP27 peptides. Reanalysis of the proteomics data from our previous studies also demonstrated that proteins from certain HSP genes could be detected simultaneously at multiple positions using SDS-PAGE, suggesting that these genes may engender multiple protein isoforms. These results collectively suggested that, besides increasing their expression, certain HSP and associated genes also use alternative transcription start sites to produce multiple RNA transcripts and use alternative splicing of a transcript to produce multiple mature RNAs, as important mechanisms for responding to an increased ambient temperature in vitro.

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Rhythm Mild‐Temperature Photothermal Therapy Enhancing Immunogenic Cell Death Response in Oral Squamous Cell Carcinoma

Ran

Liu

Song

et al. 2022

Adv Healthcare Materials

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The low antitumor efficiency and unexpected thermo‐tolerance activation of mild‐temperature photothermal therapy (mPTT) severely impede the therapeutic efficacy, thereby the implementation of reasonable mPTT procedure to improve antitumor efficiency is of great significance for clinical transformation. Herein, a rhythm mPTT with organic photothermal nanoparticles (PBDB‐T NPs) is demonstrated, synergistically increasing tumor elimination and intense immunogenic cancer cell death (ICD) to elicit tumor‐specific immune responses for tumor treatment. Specifically, PBDB‐T NPs are characterized by favorable biocompatibility, excellent and controllable photothermal properties, exhibit the properties of noninvasive diagnostic imaging, and effective mPTT against oral squamous cell carcinoma (OSCC). Encouragingly, a temperature‐dependent release of damage‐associated molecular patterns (DAMPs) is discovered during the mPTT‐induced ICD. Meanwhile, orchestrated rhythm mPTT referring to radiotherapy procedure amplifies and balances antitumor efficiency and abundant DAMPs generation to gain optimal immune activation within clinical‐recommended hyperthermia temperature compared with conventional PTT. The in vitro and in vivo results show that the rhythm mPTT unites the killing effect and ICD induction, generating strong mPTT efficacy and active tumor‐specific adaptive immune responses. The study offers a promising strategy and a new opportunity for the clinical application of mPTT.

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Hyperthermia and protein homeostasis: Cytoprotection and cell death

Cited by 55 publications

References 86 publications

Hyperthermia combined chemotherapy regulates energy metabolism of cancer cells under hypoxic microenvironment

Hyperthermia combined chemotherapy regulates energy metabolism of cancer cells under hypoxic microenvironment

At elevated temperatures, heat shock protein genes show altered ratios of different RNAs and expression of new RNAs, including several novel HSPB1 mRNAs encoding HSP27 protein isoforms

Rhythm Mild‐Temperature Photothermal Therapy Enhancing Immunogenic Cell Death Response in Oral Squamous Cell Carcinoma

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