Multidrug-resistant hela cells overexpressing MRP1 exhibit sensitivity to cell killing by hyperthermia: Interactions with etoposide

Souslova, Tatiana; Averill‐Bates, Diana A.

doi:10.1016/j.ijrobp.2004.07.686

Cited by 26 publications

(23 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These responses were, in fact, closely linked temporally. Of note, our observation of caspase-9 activation with febrile hyperthermia appears unique, as numerous other studies have used acute levels of hyperthermia [Enomoto et al, 2001;Little and Mirkes, 2002;Choi et al, 2003;Mauz-Korholz et al, 2003;Zhang et al, 2003;Souslova and Averill-Bates, 2004;Yasumoto et al, 2004]. In contrast to the role we have defined for caspase activation in this MCF-7 model, the anti-oxidant BHA was without effect on TNF killing, with or without hyperthermia ( Fig.…”

Section: Discussionmentioning

confidence: 59%

Hyperthermia engages the intrinsic apoptotic pathway by enhancing upstream caspase activation to overcome apoptotic resistance in MCF‐7 breast adenocarcinoma cells

Klostergaard¹,

LeRoux²,

Auzenne³

et al. 2006

J of Cellular Biochemistry

View full text Add to dashboard Cite

Febrile hyperthermia enhanced TNF-stimulated apoptosis of MCF-7 cells and overcame resistance in a TNF-resistant, MCF-7 variant (3E9), increasing their TNF-sensitivity by 10- and 100-fold, respectively. In either cell line, the hyperthermic potentiation was attributable to increased apoptosis that was totally quenched by caspase inhibition. In MCF-7 cells, hyperthermic potentiation of apoptosis was associated with sustained activation of upstream caspases in response to TNF and more prominent engagement of the intrinsic apoptotic pathway. Apoptotic enhancement by hyperthermia was primarily mediated by caspase-8 activation, as the specific inhibitor, Z-IETD, blocked cell death, whereas direct engagement of the intrinsic apoptotic pathway (with doxorubicin) was not affected. In 3E9 cells, hyperthermia alone induced activation of caspase-8, and was further enhanced by TNF. In 3E9 cells, hyperthermia caused TNF-dependent loss of mitochondrial membrane potential and activation of capspase-9 that was initiated and dependent on upstream caspases. MCF-7 and 3E9 cells were equally sensitive to exogenous C(6)-ceramide, but mass spectroscopic analysis of ceramide species indicated that total ceramide content was not enhanced by TNF and/or hyperthermia treatment, and that the combination of TNF and hyperthermia caused only modest elevation of one species (dihydro-palmitoyl ceramide). We conclude that febrile hyperthermia potentiates apoptosis of MCF-7 cells and overcomes TNF-resistance by sustained activation of caspase-8 and engagement of the intrinsic pathway that is independent of ceramide flux. This report provides the first evidence for regulation of caspase-dependent apoptosis by febrile hyperthermia.

show abstract

Section: Discussionmentioning

confidence: 59%

Hyperthermia engages the intrinsic apoptotic pathway by enhancing upstream caspase activation to overcome apoptotic resistance in MCF‐7 breast adenocarcinoma cells

Klostergaard¹,

LeRoux²,

Auzenne³

et al. 2006

J of Cellular Biochemistry

View full text Add to dashboard Cite

show abstract

“…A combination of hyperthermia with radiotherapy and chemotherapy has been clinically applied for various solid tumors [1–3]. Thus, the biological effects of hyperthermia have been extensively studied.…”

Section: Introductionmentioning

confidence: 99%

The Role of Mitochondria-Derived Reactive Oxygen Species in Hyperthermia-Induced Platelet Apoptosis

et al. 2013

View full text Add to dashboard Cite

A combination of hyperthermia with radiotherapy and chemotherapy for various solid tumors has been practiced clinically. However, hyperthermic therapy has side effects, such as thrombocytopenia. Up to now, the pathogenesis of hyperthermia-induced thrombocytopenia remains unclear. Previous studies have shown that hyperthermia induces platelet apoptosis. However, the signaling pathways and molecular mechanisms involved in hyperthermia-induced platelet apoptosis have not been determined. Here we show that hyperthermia induced intracellular reactive oxygen species (ROS) production and mitochondrial ROS generation in a time-dependent manner in platelets. The mitochondria-targeted ROS scavenger Mito-TEMPO blocked intracellular ROS and mitochondrial ROS generation. By contrast, inhibitors of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, nitric oxide synthase, cyclooxygenase and lipoxygenase did not. Furthermore, Mito-TEMPO inhibited hyperthermia-induced malonyldialdehyde production and cardiolipin peroxidation. We also showed that hyperthermia-triggered platelet apoptosis was inhibited by Mito-TEMPO. Furthermore, Mito-TEMPO ameliorated hyperthermia-impaired platelet aggregation and adhesion function. Lastly, hyperthermia decreased platelet manganese superoxide dismutase (MnSOD) protein levels and enzyme activity. These data indicate that mitochondrial ROS play a pivotal role in hyperthermia-induced platelet apoptosis, and decreased of MnSOD activity might, at least partially account for the enhanced ROS levels in hyperthermia-treated platelets. Therefore, determining the role of mitochondrial ROS as contributory factors in platelet apoptosis, is critical in providing a rational design of novel drugs aimed at targeting mitochondrial ROS. Such therapeutic approaches would have potential clinical utility in platelet-associated disorders involving oxidative damage.

show abstract

“…Classical paradigms suggest that hyperthermia (and in particular, temperatures over 42°C) has the ability to sensitize radioresistant tumor cells to apoptosis [9]. Hyperthermia also interferes with DNA damage repair [10], augments drug uptake into tumor cells and can reverse drug resistance [11,12]. However, there has long been appreciation in this field of the potential similarity between exogenously induced hyperthermia used in the clinic and natural hyperthermic states which occur during fever.…”

Section: Introductionmentioning

confidence: 99%

Diverse immune mechanisms may contribute to the survival benefit seen in cancer patients receiving hyperthermia

et al. 2009

View full text Add to dashboard Cite

There is increasing documentation of significant survival benefits achieved in cancer patients treated with hyperthermia in combination with radiation and/or chemotherapy. Most evidence collected regarding the mechanisms by which hyperthermia positively influences tumor control has centered on in vitro data showing the ability of heat shock temperatures (usually above 42 degrees C) to result in radio- or chemosensitization. However, these high temperatures are difficult to achieve in vivo, and new thermometry data in patients reveal that much of the tumor and surrounding region is only heated to 40-41 degrees C or less as a result of vascular drainage from the target zone of the heated tumor. Thus, there is now a growing appreciation of a role for mild hyperthermia in the stimulation of various arms of the immune system in contributing to long term protection from tumor growth. Indeed, a review of recent literature suggests the existence of an array of thermally sensitive functions which may exist naturally to help the organism to establish a new "set point" of immune responsiveness during fever. This review summarizes recent literature identifying complex effects of temperature on immune cells and potential cellular mechanisms by which increased temperature may enhance immune surveillance.

show abstract

Multidrug-resistant hela cells overexpressing MRP1 exhibit sensitivity to cell killing by hyperthermia: Interactions with etoposide

Cited by 26 publications

References 59 publications

Hyperthermia engages the intrinsic apoptotic pathway by enhancing upstream caspase activation to overcome apoptotic resistance in MCF‐7 breast adenocarcinoma cells

Hyperthermia engages the intrinsic apoptotic pathway by enhancing upstream caspase activation to overcome apoptotic resistance in MCF‐7 breast adenocarcinoma cells

The Role of Mitochondria-Derived Reactive Oxygen Species in Hyperthermia-Induced Platelet Apoptosis

Diverse immune mechanisms may contribute to the survival benefit seen in cancer patients receiving hyperthermia

Contact Info

Product

Resources

About