Heat stress induced cell death mechanisms in hepatocytes and hepatocellular carcinoma: In vitro and in vivo study

Thompson, Scott M.; Callstrom, Matthew R.; Butters, Kim A.; Knudsen, Bruce E.; Grande, Joseph P.; Roberts, Lewis R.; Woodrum, David A.

doi:10.1002/lsm.22231

Cited by 32 publications

(35 citation statements)

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“…Several conditions, molecules, and organelles may be involved in apoptosis and ROS may play a key role in apoptosis (Wang et al, 2008). Our finding are in agreement with previous studies reporting that heat stress induced apoptosis in chicken myocardial cells (Xu et al, 2017), human umbilical vein endothelial cells (Li et al, 2015)hepatocytes and hepatocellular carcinoma cells (Thompson et al, 2014), and rat germ cells (Lizama et al, 2009).…”

Section: The Effect Of High Temperature On Viability Proliferation supporting

confidence: 93%

The Effect of High Temperature on Viability, Proliferation, Apoptosis and Anti-oxidant Status of Chicken Embryonic Fibroblast Cells

Ibtisham

Yun-feng

Nawab

et al. 2018

Braz. J. Poult. Sci.

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The effects of oxidative stress induced by high temperature on the cell viability, proliferation, apoptosis and oxidative status of chicken embryonic fibroblasts (CEF) were analyzed. The viability, proliferation, apoptotic and anti-oxidative status were measured after incubating CEF at the temperatures of 37ºC (control) and 40-44ºC (experimental groups) for 6,12 and 24 hours. The results showed that at high temperature (42-43ºC), the viability of CEF cells decreased after 6, 12 and 24 h of incubation, but the difference was significant only at 43ºC. Cell proliferation was significantly reduced at 44 o C/6h. The apoptotic rate of CEF cells was increased following heat treatments in a time-dependent manner. ROS formation increased with increasing temperature, but the difference was only significant at 44ºC/6,12h. Heat stress did not significantly affect the superoxide dismutase (SOD) activity. CAT activity was significantly decreased at 43ºC/24h and 44ºC/12 and 24h. Malondialdehyde (MDA) formation was significantly increased at 43ºC/12h and 44ºC/12 and 24h. In conclusion, heat stress induced the oxidative stress, decreasing the viability, proliferation and anti-oxidative response of CEF cells.

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Section: The Effect Of High Temperature On Viability Proliferation supporting

confidence: 93%

The Effect of High Temperature on Viability, Proliferation, Apoptosis and Anti-oxidant Status of Chicken Embryonic Fibroblast Cells

Ibtisham

Yun-feng

Nawab

et al. 2018

Braz. J. Poult. Sci.

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“…Cellular heat stress protocol.-Cell lines were suspended in complete media in microcentrifuge tubes and were heat stressed for 10 minutes with moderate (45°C), severe (50°C), or physiologic (37°C) heat stress in an isothermic water bath (Appendix E1 [online]) (18,24).…”

Section: Methodsmentioning

confidence: 99%

“…These findings are generalizable to a subset of HCCs with a more aggressive phenotype and laser ablation. The N1S1 and AS30D models were chosen because of their biologic relevance to two different human HCC subtypes, as well as the PI3K/mTOR/AKT pathway (18,24,27,44). However, further studies are needed in additional preclinical HCC models with different host tumor microenvironments and immune statuses and with different ablation devices to better understand the generalizability of these findings (37,(44)(45)(46).…”

Section: Genementioning

confidence: 99%

“…The N1S1 orthotopic HCC model was developed in male Sprague-Dawley rats (Harlan/Envigo Laboratories, Indianapolis, Indiana) (weight range, 400-500 g) (27). Immediately after injection of N1S1 cells (3 3 10 6 cells) into the median hepatic lobe, rats were randomly assigned to undergo hepatic laser ablation in the HCC cell-bearing median hepatic lobe (local) or left lateral hepatic lobe (distant) with an energy dose of 3 W for 60 or 90 seconds (hereafter, 3W360s and 3W390s, respectively) or sham ablation with a Food and Drug Administration-approved 980-nm laser generator (Visualase, Houston, Tex) (six or more rats per experimental group) (24,25,27). The laser fiber was inserted but not activated in sham-ablated animals.…”

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confidence: 99%

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Heat Stress and Hepatic Laser Thermal Ablation Induce Hepatocellular Carcinoma Growth: Role of PI3K/mTOR/AKT Signaling

et al. 2018

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Purpose To determine if heat stress and hepatic laser thermal ablation induce hepatocellular carcinoma (HCC) growth and to identify growth factors induced by heat stress. Materials and Methods Non-heat-stressed HCC cells were cocultured with HCC cells or hepatocytes that were heat stressed at 37°C (physiologic), 45°C (moderate), or 50°C (severe) for 10 minutes and proliferation monitored with bioluminescence imaging for up to 6 days after heat stress (three experiments). Rats bearing orthotopic N1S1 HCC were randomly assigned to undergo immediate sham or laser thermal (3 W for 60 or 90 seconds; hereafter, 3W×60s and 3W×90s, respectively) ablation of the median (local) or left (distant) hepatic lobe, and tumor growth was monitored with magnetic resonance imaging for up to 18 days after ablation (six or more rats per group). Experiments were repeated with rats randomly assigned to receive either the adjuvant phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor (NVP-BEZ235) or the vehicle control. Heat-stressed HCC cells and hepatocytes were analyzed by using microarray or quantitative real-time polymerase chain reaction analysis for growth factor expression (three or more experiments). Groups were compared by using one- or two-way analysis of variance, and post hoc pairwise comparison was performed with the Dunnett test. Results There were more non-heat-stressed HCC cells when cells were cocultured with cells subjected to moderate but not physiologic or severe heat stress (P < .001 for both). Local intrahepatic N1S1 tumors were larger at day 18 in the 3W×60s (mean, 3102 mm ± 463 [standard error]; P = .004) and 3W×90s (mean, 3538 mm ± 667; P < .001) groups than in the sham group (mean, 1363 mm ± 361) but not in distant intrahepatic tumors (P = .31). Adjuvant BEZ235 resulted in smaller N1S1 tumors in the BEZ235 and laser thermal ablation group than in the vehicle control and laser thermal ablation group (mean, 1731 mm ± 1457 vs 3844 mm ± 2400, P < .001). Moderate heat stress induced expression of growth factors in HCC cells and hepatocytes, including heparin-binding growth factor, fibroblast growth factor 21, and nerve growth factor (range, 2.9-66.9-fold; P < .05). Conclusion Moderate heat stress and laser thermal ablation induce hepatocellular carcinoma growth, which is prevented with adjuvant PI3K/mTOR/protein kinase B inhibition.

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“…Ablation and embolization are the two most common minimally invasive methods of treating unresectable hepatocellular carcinoma (HCC). However, incomplete ablation is more prevalent than commonly believed [1,2]. Total necrosis rates are less than 50% in treated nodules.…”

Section: Introductionmentioning

confidence: 99%

A molecular dynamics approach towards evaluating osmotic and thermal stress in the extracellular environment

Fuentes

Muñoz

Guo

et al. 2018

International Journal of Hyperthermia

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Objective: A molecular dynamics approach to understanding fundamental mechanisms of combined thermal and osmotic stress induced by thermochemical ablation (TCA) is presented. Methods: Structural models of fibronectin and fibronectin bound to its integrin receptor provide idealized models for the effects of thermal and osmotic stress in the extracellular matrix. Fibronectin binding to integrin is known to facilitate cell survival. The extracellular environment produced by TCA at the lesion boundary was modelled at 37 C and 43 C with added sodium chloride (NaCl) concentrations (0, 40, 80, 160, and 320 mM). Atomistic simulations of solvated proteins were performed using the GROMOS96 force field and TIP3P water model. Computational results were compared with the results of viability studies of human hepatocellular carcinoma (HCC) cell lines HepG2 and Hep3B under matching thermal and osmotic experimental conditions. Results: Cell viability was inversely correlated with hyperthermal and hyperosmotic stresses. Added NaCl concentrations were correlated with a root mean square fluctuation increase of the fibronectin arginylglycylaspartic acid (RGD) binding domain. Computed interaction coefficients demonstrate preferential hydration of the protein model and are correlated with salt-induced strengthening of hydrophobic interactions. Under the combined hyperthermal and hyperosmotic stress conditions (43 C and 320 mM added NaCl), the free energy change required for fibronectin binding to integrin was less favorable than that for binding under control conditions (37 C and 0 mM added NaCl). Conclusion: Results quantify multiple measures of structural changes as a function of temperature increase and addition of NaCl to the solution. Correlations between cell viability and stability measures suggest that protein aggregates, non-functional proteins, and less favorable cell attachment conditions have a role in TCA-induced cell stress. ARTICLE HISTORY

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Heat stress induced cell death mechanisms in hepatocytes and hepatocellular carcinoma: In vitro and in vivo study

Cited by 32 publications

References 50 publications

The Effect of High Temperature on Viability, Proliferation, Apoptosis and Anti-oxidant Status of Chicken Embryonic Fibroblast Cells

The Effect of High Temperature on Viability, Proliferation, Apoptosis and Anti-oxidant Status of Chicken Embryonic Fibroblast Cells

Heat Stress and Hepatic Laser Thermal Ablation Induce Hepatocellular Carcinoma Growth: Role of PI3K/mTOR/AKT Signaling

A molecular dynamics approach towards evaluating osmotic and thermal stress in the extracellular environment

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