Carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP) as an O2− generator induces apoptosis via the depletion of intracellular GSH contents in Calu-6 cells

Han, Yong Hwan; Kim, Suhn Hee; Kim, Sung Zoo; Park, Woo Hyun

doi:10.1016/j.lungcan.2008.05.005

Cited by 56 publications

(53 citation statements)

References 49 publications

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“…Our observations confirmed that FCCP can depolarize the mitochondrial membrane potential within minutes [15,20]. Importantly, transient depolarization (or Bmild uncoupling^) of the mitochondrial membrane potential then can linger on for 30 min [15] or up to 72 h [19]. This phenomenon was shown to protect cells against toxicity [15].…”

Section: Discussionsupporting

confidence: 79%

“…Mitochondrial membrane potential was assessed according to previous studies [19][20][21]. In brief, the tissue fragments were incubated with holding medium supplemented with 10 μg/mL rhodamine 123 (Invitrogen), a cell-permeable cationic dye that preferentially enters mitochondria based on a highly negative mitochondrial membrane potential.…”

Section: Mitochondrial Membrane Potential Assessmentmentioning

confidence: 99%

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Carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) pre-exposure ensures follicle integrity during in vitro culture of ovarian tissue but not during cryopreservation in the domestic cat model

Tanpradit

Chatdarong

Comizzoli

2016

J Assist Reprod Genet

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Purpose Temporary and reversible downregulation of metabolism may improve the survival of tissues exposed to nonphysiological conditions during transport, in vitro culture, and cryopreservation. The objectives of the study were to (1) optimize the concentration and duration of carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP-a mitochondrial uncoupling agent) exposures for biopsies of domestic cat ovarian tissue and (2) examine the effects of FCCP preexposures on follicle integrity after tissue culture and/or cryopreservation. Methods Biopsies of cat ovarian tissue were first treated with various concentrations of FCCP (0, 10, 40, or 200 nM) for 10 or 120 min to determine the most suitable pre-exposure conditions. Based on these results, tissues were pre-exposed to 200 nM FCCP for 120 min for the subsequent studies on culture and cryopreservation. In all experiments and for each treatment group, tissue activity and integrity were measured by mitochondrial membrane potential (relative optical density of rhodamine 123 fluorescence), follicular viability (calcein assay), follicular morphology (histology), granulosa cell proliferation (Ki-67 immunostaining), and follicular density.Results Ovarian tissues incubated with 200 nM FCCP for 120 min led to the lowest mitochondrial activity (1.17 ± 0.09; P < 0.05) compared to control group (0 nM; 1.30 ± 0.12) while maintaining a constant percentage of viable follicles (75.3 ± 7.8 %) similar to the control group (71.8 ± 11.7 %; P > 0.05). After 2 days of in vitro culture, percentage of viable follicles (78.8 ± 8.9 %) in similar pre-exposure conditions was higher (P < 0.05) than in the absence of FCCP (61.2 ± 12.0 %) with percentages of morphologically normal follicles (57.6 ± 17.3 %) not different from the fresh tissue (70.2 ± 7.1 %; P > 0.05). Interestingly, percentages of cellular proliferation and follicular density were unaltered by the FCCP exposures. Based on the indicators mentioned above, the FCCP-treated tissue fragments did not have a better follicle integrity after freezing and thawing. Conclusions Pre-exposure to 200 nM FCCP during 120 min protects and enhances the follicle integrity in cat ovarian tissue during short-term in vitro culture. However, FCCP does not appear to exert a beneficial or detrimental effect during ovarian tissue cryopreservation.

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Section: Discussionsupporting

confidence: 79%

Section: Mitochondrial Membrane Potential Assessmentmentioning

confidence: 99%

Carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) pre-exposure ensures follicle integrity during in vitro culture of ovarian tissue but not during cryopreservation in the domestic cat model

Tanpradit

Chatdarong

Comizzoli

2016

J Assist Reprod Genet

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“…Although chemical uncouplers are known to decrease ROS production in isolated mitochondria (30,31), there are reports that the uncouplers rather increase mitochondrial ROS production in cells through hypoxia and HIF-1α activity (32)(33)(34). We thus tested the effect of carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP) and 2,4-dinitrophenol (DNP), and compared with oligomycin (an ATP synthase inhibitor) as control.…”

Section: Resultsmentioning

confidence: 99%

Mitochondrial activation chemicals synergize with surface receptor PD-1 blockade for T cell-dependent antitumor activity

Chamoto

Chowdhury

Kumar

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

313

287

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Although immunotherapy by PD-1 blockade has dramatically improved the survival rate of cancer patients, further improvement in efficacy is required to reduce the fraction of less sensitive patients. In mouse models of PD-1 blockade therapy, we found that tumor-reactive cytotoxic T lymphocytes (CTLs) in draining lymph nodes (DLNs) carry increased mitochondrial mass and more reactive oxygen species (ROS). We show that ROS generation by ROS precursors or indirectly by mitochondrial uncouplers synergized the tumoricidal activity of PD-1 blockade by expansion of effector/ memory CTLs in DLNs and within the tumor. These CTLs carry not only the activation of mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) but also an increment of their downstream transcription factors such as PPAR-gamma coactivator 1α (PGC-1α) and T-bet. Furthermore, direct activators of mTOR, AMPK, or PGC-1α also synergized the PD-1 blockade therapy whereas none of above-mentioned chemicals alone had any effects on tumor growth. These findings will pave a way to developing novel combinatorial therapies with PD-1 blockade.PD-1 | cancer immunotherapy | mitochondria | immune metabolism | PGC-1α

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“…MMP (ΔΨ m ) levels were measured using a rhodamine 123 fluorescent dye (Sigma-Aldrich; Merck KGaA; Ex/Em=485/535 nm) as previously described (28,30,31). Briefly, 1x10 6 HPF cells in 60 mm culture plates (Nalge Nunc International; Thermo Fisher Scientific, Inc.) were incubated with 0, 50 or 100 µM PG in the presence or absence of each MAPK inhibitor at 37˚C for 24 h. Rhodamine 123 staining intensity was determined using a FACStar flow cytometer (BD Biosciences) and CellQuest Pro software (version 5.1; BD Biosciences).…”

Section: Measurement Of Mitochondrial Membrane Potential (Mmp; δψ M )mentioning

confidence: 99%

MAPK inhibitors enhance cell death in pyrogallol-treated human pulmonary fibroblast cells via increasing O2•− levels

Han

Park

2017

Oncology Letters

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Abstract. Pyrogallol (PG) induces apoptosis in lung cancer cells via the overproduction of O 2•-and affects mitogen-activated protein kinases (MAPKs) in these cells. The aim of the present study was to elucidate the effect of PG and/or MAPK inhibitors on human pulmonary fibroblast (HPF) cell viability in relation to reactive oxygen species (ROS) and glutathione (GSH). Treatment with 50 or 100 µM PG inhibited the viability of HPF cells, and induced cell death and the loss of mitochondrial membrane potential (MMP; ΔΨ m ). In particular, treatment with 100 µM PG induced cell death via apoptosis as well as necrosis in HPF cells. PG increased mitochondrial O 2•-levels and the number of GSH-depleted HPF cells. All the MAPK (mitogen-activated protein kinase kinase, c-Jun N-terminal kinase and p38) inhibitors enhanced the inhibition of cell viability, cell death and MMP (ΔΨ m ) loss in 100 µM PG-treated HPF cells. All the inhibitors increased the O 2•-levels in 100 µM PG-treated HPF cells, but none of the inhibitors significantly altered the PG-induced GSH depletion. In conclusion, PG treatment induced cell death via apoptosis and necrosis in HPF cells. Treatment with MAPK inhibitors slightly enhanced cell death in PG-treated HPF cells. HPF cell death induced by PG and/or MAPK inhibitors was at least partially associated with changes in O 2•-levels and GSH content. The present data provided useful information to understand PG-induced normal lung cell death in association with MAPK signaling pathways and ROS levels.

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Carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP) as an O2− generator induces apoptosis via the depletion of intracellular GSH contents in Calu-6 cells

Cited by 56 publications

References 49 publications

Carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) pre-exposure ensures follicle integrity during in vitro culture of ovarian tissue but not during cryopreservation in the domestic cat model

Carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) pre-exposure ensures follicle integrity during in vitro culture of ovarian tissue but not during cryopreservation in the domestic cat model

Mitochondrial activation chemicals synergize with surface receptor PD-1 blockade for T cell-dependent antitumor activity

MAPK inhibitors enhance cell death in pyrogallol-treated human pulmonary fibroblast cells via increasing O2•− levels

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