Hyperthermia Induces Apoptosis of 786-O Cells through Suppressing Ku80 Expression

Qi, Defeng; Hu, Yuan; Li, Jinhui; Peng, Tao; Su, Jialin; He, Yun; Ji, Weidong

doi:10.1371/journal.pone.0122977

Cited by 19 publications

(19 citation statements)

References 42 publications

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“…Analysis of cell cycle revealed increased presence of HT29 cells in G 2 /M phase after heat shock application, while combination of hyperthermia with auraptene resulted in considerable accumulation of cells in sub G 1 /G 1 phase. In consistence with our findings, G 2 /M phase arrest was reported after hyperthermia in several cell types such as liver, lung, breast and renal cancer cells (Qi et al 2015;Zhao et al 2015;Yan et al 2014;Lin et al 2013). Same as present results, previous studies have also indicated growth controlling effects of auraptene on breast and gastric carcinoma cells by cell cycle arrest in sub G 1 (Mousavi et al 2015, Moon et al 2015 and G 0 -G 1 phases (de Medina et al 2010;Krishnan et al 2009).…”

Section: R a F Tsupporting

confidence: 91%

Efficacy of hyperthermia in human colon adenocarcinoma cells is improved by auraptene

Moussavi

Haddad

Matin

et al. 2018

Biochem. Cell Biol.

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Colon adenocarcinoma is one of the most common cancers worldwide, and resistance to current therapeutic modalities is a serious drawback in its treatment. Auraptene is a natural coumarin with considerable anticancer effects. The goal of this study was to introduce a novel combinatorial approach for treatment against colon adenocarcinoma cells. To do so, HT29 cells were pretreated with nontoxic auraptene and then hyperthermia was induced. Afterwards, the viability of the cells was assessed, changes induced in the cell cycle were analyzed, and the expression patterns of candidate genes were studied. Results from the MTT assay demonstrated significant (p < 0.01) decreases in cell viability when 20 μg/mL auraptene was used for 72 h, heat shock was induced, and cells were allowed to recover for 24 h. Flow cytometry analysis also indicated considerable changes in the distribution of cells between the sub-G/G and G/M phases of cell cycle after the combinatorial treatment. Real-time RT-PCR studies revealed significant (p < 0.01) up-regulation of P21 in the cells pretreated with auraptene after heat shock, whereas no significant change was observed in HSP27 expression. Our findings not only indicate, for the first time, that the efficacy of hyperthermia was improved by auraptene pretreatment, but also suggest that this coumarin could be used in the future to achieve more effective therapeutic outcomes.

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Section: R a F Tsupporting

confidence: 91%

Efficacy of hyperthermia in human colon adenocarcinoma cells is improved by auraptene

Moussavi

Haddad

Matin

et al. 2018

Biochem. Cell Biol.

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“…In addition to surgery, chemotherapy, radiation and biological therapy, hyperthermia has become a leading strategy for the treatment of cancer, and is a key part of multidisciplinary therapy ( 9 ). In RCC, hyperthermia is accepted as an alternative method to surgery in certain patients who are not suitable as surgical candidates ( 22 ).…”

Section: Discussionmentioning

confidence: 99%

“…The potential mechanisms regarding inhibited proliferation are considered to involve the suppression of tumor cell replication and metabolism. For instance, in the renal cell carcinoma (RCC) cell line 786-O, hyperthermia exposure suppressed Ku80 expression and lead to G2/M phase cell cycle arrest, which may represent a potential mechanism of hyperthermia-mediated suppression of proliferation ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

Hyperthermia exposure induces apoptosis and inhibits proliferation in HCT116 cells by upregulating miR‑34a and causing transcriptional activation of p53

et al. 2017

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Hyperthermia, as an anticancer therapeutic strategy, presents notable advantages in conjunction with irradiation and/or chemotherapy in the treatment of cancer by promoting apoptosis and inhibiting proliferation. A number of studies have documented that hyperthermia inhibits cancer progression through transcriptional activation of p53, which promotes cell cycle arrest and apoptosis. However, the underlying molecular mechanisms of hyperthermia-regulated apoptosis and proliferation dependent on p53 remain largely unknown. To investigate the effects and molecular mechanism of hyperthermia on the apoptosis and proliferation of colorectal carcinoma (CRC) HCT116 cells, the present study assessed cell apoptosis and proliferation following exposure to hyperthermia (42°C for 2–4 h). The results indicated that, compared with the control group at 0 h, hyperthermia exposure for 2 and 4 h induced the apoptosis of HCT116 cells (P<0.05), inhibited cell proliferation by causing cell cycle arrest at G1/G0 phase (P<0.05), and significantly increased microRNA (miR)-34a expression (P<0.05), but not miR-34b, miR-34c, miR-215 and miR-504 expression. The transcriptional activity of p53 on its consensus sequence and downstream target genes, namely p21, B cell lymphoma 2-associated X protein, mouse double minute 2 homolog, p53 upregulated modulator of apoptosis and growth arrest and DNA-damage-inducible 45α, was subsequently detected. The data indicated significantly higher transcriptional activity of p53 following hyperthermia exposure for 2 and 4 h (P<0.05), and these observations were similar to the effects of transfection with miR-34a mimics in HCT116 cells. Furthermore, transfection with miR-34a antagomiR supressed hyperthermia-induced apoptosis and promoted cell cycle progression following hyperthermia exposure when compared with transfection controls (P<0.05). Collectively, these findings indicate that miR-34a may serve an important role in hyperthermia-regulated apoptosis and proliferation in HCT116 cells by influencing the transcriptional activity of p53.

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“…Apoptosis is the autonomous process of programmed cell death controlled by gene expression, which functions to regulate and maintain a stable internal environment in multicellular organisms. Previous studies have demonstrated that hyperthermia induces apoptosis in tumor cells (4,8,9). Hyperthermia at 40-45˚C was observed to induce apoptosis-mediated cell death in tumor cells, with no significant influence on normal tissues, while hyperthermia at temperatures >45˚C was identified to induce necrosis-mediated cell death with additional damage to normal tissues (10,11).…”

Section: Introductionmentioning

confidence: 94%

Identification of proteins interacting with protein kinase C-δ in hyperthermia-induced apoptosis and thermotolerance of Tca8113 cells

Liu

Huang

Lin

et al. 2015

Molecular Medicine Reports

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The purpose of the present study was to investigate the differential proteins that interact with protein kinase C‑δ (PKC‑δ) in hyperthermia‑induced apoptosis as well as thermotolerance in Tca8113 cells, and furthermore, to investigate the mechanisms of these processes in tumor cells. Activation of PKC‑δ was previously indicated to be involved in the heat sensitivity and thermal resistance of tongue squamous carcinoma cells. Tca8113 cell apoptosis was induced by incubation at 43˚C for 80 min and the thermotolerant Tca8113 cells (TT‑Tca8113) were generated through a gradient temperature‑elevating method. The apoptotic rate of the cells was determined by flow cytometry, while cleavage and activation of PKC‑δ were analyzed by western blot analysis. The proteins that interacted with PKC‑δ in the Tca8113 and TT‑Tca8113 cells were identified by co‑immunoprecipitation coupled with mass spectrometry. Co‑immunoprecipitation analysis followed by electrospray ionization mass spectrometric analysis were utilized to identify the pro‑ and anti‑apoptotic proteins that interacted with PKC‑δ. Significant cell apoptosis was observed in Tca8113 cells following hyperthermia, and the apoptotic rate was significantly higher than that in the control group (P<0.05). Marked PKC‑δ cleavage fragmentation was also identified. By contrast, the apoptotic rate of the TT‑Tca8113 cells was not significantly increased following hyperthermia and no PKC‑δ cleavage fragmentation was observed. Among the proteins interacting with PKC‑δ, 39 were found to be involved in the promotion of apoptosis and 16 in the inhibition of apoptosis of Tca8113 cells; these proteins were known to be involved in the regulation of cell proliferation, apoptosis, transcription and intracellular protein transport. The results of the present study provided evidence that PKC‑δ is a crucial factor in the heat sensitivity and thermal resistance of tongue squamous carcinoma cells and elucidated the underlying molecular basis, which may aid in the improvement of hyperthermic cancer treatments.

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Hyperthermia Induces Apoptosis of 786-O Cells through Suppressing Ku80 Expression

Cited by 19 publications

References 42 publications

Efficacy of hyperthermia in human colon adenocarcinoma cells is improved by auraptene

Efficacy of hyperthermia in human colon adenocarcinoma cells is improved by auraptene

Hyperthermia exposure induces apoptosis and inhibits proliferation in HCT116 cells by upregulating miR‑34a and causing transcriptional activation of p53

Identification of proteins interacting with protein kinase C-δ in hyperthermia-induced apoptosis and thermotolerance of Tca8113 cells

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