Silver nanoparticles induce apoptotic cell death in <i>Candida albicans</i> through the increase of hydroxyl radicals

Hwang, In-sok; Lee, Jun-Young; Hwang, Jun Hyun; Kim, Keuk‐Jun; Lee, Dong Gun

doi:10.1111/j.1742-4658.2012.08527.x

Cited by 210 publications

(168 citation statements)

References 48 publications

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“…The ability of AgNPs to generate such species led to phosphatidylserine externalization, DNA and nuclear fragmentation, mitochondria dysfunction, and caspase activity in cancer cells. 42,[46][47][48] The results suggest that the mode of cell death induced coincides with that found during photodynamic therapy. Although cell death due to photothermal effects has been identified, 49 the laser irradiation applied during this study does not support the induction of thermal effects.…”

supporting

confidence: 55%

Photodynamic ability of silver nanoparticles in inducing cytotoxic effects in breast and lung cancer cell lines

Elhussein¹,

Harith²,

Abrahamse³

et al. 2014

IJN

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supporting

confidence: 55%

Photodynamic ability of silver nanoparticles in inducing cytotoxic effects in breast and lung cancer cell lines

Elhussein¹,

Harith²,

Abrahamse³

et al. 2014

IJN

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“…As high temperatures induce both apoptosis and necrosis in mammalian cells (15), we sought to differentiate between apoptotic and necrotic R. oryzae cells by using the annexin V-FITC and PI double-staining method. In this method, apoptotic cells are stained with annexin V-FITC, whereas PI accumulates in the nuclei of necrotic cells via membrane permeabilization (34). Following PCZ (0.25 g/ml) and ICZ (0.5 g/ml) exposure at 42°C, 65% to 76% of the cells were stained with annexin V-FITC, while only 6% to 26% and 19% to 73% of the cells were stained with annexin V-FITC at 25°C (PCZ or ICZ at 8 to 16 g/ml) and 37°C (PCZ or ICZ at 4 to 8 g/ml), respectively (Fig.…”

Section: Resultsmentioning

confidence: 99%

Hyperthermia Sensitizes Rhizopus oryzae to Posaconazole and Itraconazole Action through Apoptosis

Shirazi

Pontikos

Walsh

et al. 2013

Antimicrob Agents Chemother

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The high mortality rate of mucormycosis with currently available monotherapy has created interest in studying novel strategies for antifungal agents. With the exception of amphotericin B (AMB), the triazoles (posaconazole [PCZ] and itraconazole [ICZ]) are fungistatic in vitro against Rhizopus oryzae. We hypothesized that growth at a high temperature (42°C) results in fungicidal activity of PCZ and ICZ that is mediated through apoptosis. R. oryzae had high MIC values for PCZ and ICZ (16 to 64 g/ml) at 25°C; in contrast, the MICs for PCZ and ICZ were significantly lower at 37°C (8 to 16 g/ml) and 42°C (0.25 to 1 g/ml). Furthermore, PCZ and ICZ dose-dependent inhibition of germination was more pronounced at 42°C than at 37°C. In addition, intracellular reactive oxygen species (ROS) increased significantly when fungi were exposed to antifungals at 42°C. Characteristic cellular changes of apoptosis in R. oryzae were induced by the accumulation of intracellular reactive oxygen species. Cells treated with PCZ or ICZ in combination with hyperthermia (42°C) exhibited characteristic markers of early apoptosis: phosphatidylserine externalization visualized by annexin V staining, membrane depolarization visualized by bis-[1,3-dibutylbarbituric acid] trimethine oxonol (DiBAC) staining, and increased metacaspase activity. Moreover, terminal deoxynucleotidyltransferasemediated dUTP-biotin nick end labeling (TUNEL) assay and DAPI (4=,6-diamidino-2-phenylindole) staining demonstrated DNA fragmentation and condensation, respectively. The addition of N-acetylcysteine increased fungal survival, prevented apoptosis, reduced ROS accumulation, and decreased metacaspase activation. We concluded that hyperthermia, either alone or in the presence of PCZ or ICZ, induces apoptosis in R. oryzae. Local thermal delivery could be a therapeutically useful adjunct strategy for these refractory infections.

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“…Taken together, therefore, the data suggest that caspofungin at concentrations below the MIC causes C. albicans cells to undergo apoptosis but that increasing caspofungin concentrations above the MIC does not further induce programmed cell death responses. Previous studies have shown that several stimuli, including acetic acid (7), hydrogen peroxide (27), 1,10-phenanthroline metal complexes (28), silver-coumarin complexes (17), diallyl disulfide (29), farsenol (26), lactoferrin (30), defensins (31), and the antifungal agent amphotericin B (9), cause C. albicans cells to undergo apoptosis. Our data demonstrate that cell wall stress stemming from inhibition of (1,3)-␤-D-glucan, as caused by caspofungin and Zymolyase (at concentrations Ն0.1 mg/ml), is also a trigger for apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…We utilized terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and 4=,6-diamidino-2-phenylindole dihydrochloride (DAPI) staining. For TUNEL assays, protoplasts were prepared as described above (7,17). TUNEL reactions were carried out by using the in situ cell death detection kit (Roche Applied Science) (18).…”

Section: Methodsmentioning

confidence: 99%

Caspofungin Kills Candida albicans by Causing both Cellular Apoptosis and Necrosis

Hao

Cheng

Clancy

et al. 2013

Antimicrob Agents Chemother

152

132

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Caspofungin exerts candidacidal activity by inhibiting cell wall (1,3)-␤-D-glucan synthesis. We investigated the physiologic mechanisms of caspofungin-induced Candida albicans cell death. Apoptosis (programmed cell death) and necrosis were studied after C. albicans SC5314 cells were exposed to caspofungin at 0.06, 0.125, and 0.5 g/ml (0.5؋, 1؋, and 4؋ the MIC, respectively) for 3 h. Caspofungin at 0.125 and 0.5 g/ml reduced cellular viability by >50%, as measured by colony counts and methylene blue exclusion. Apoptosis and necrosis were demonstrated by annexin V and propidium iodide staining for phosphatidylserine externalization and loss of membrane integrity, respectively. At all concentrations of caspofungin, 20 to 25% and 5 to 7% of C. albicans cells exhibited early apoptosis and late apoptosis/necrosis, respectively (P value was not significant [NS]). Necrosis, on the other hand, was significantly greater at 0.125 (43%) and 0.5 (48%) g/ml than at 0.06 g/ml (26%) (P values of 0.003 and 0.003, respectively). The induction of apoptosis at concentrations less than or equal to the MIC was corroborated by dihydrorhodamine 123 (DHR-123) and dihydroethidium (DHE) staining (reactive oxygen species production), JC-1 staining (mitochondrial membrane potential dissipation), and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and 4=,6-diamidino-2-phenylindole dihydrochloride (DAPI) staining (DNA damage and nuclear fragmentation). Moreover, electron microscopy of cells exposed to 0.125 g/ml of caspofungin showed hallmark apoptotic features like chromatin margination and condensation and nuclear blebs. Apoptosis was associated with metacaspase 1 activation, as demonstrated by D2R staining. Caspofungin exerts activity against C. albicans by directly killing cells (resulting in necrosis) and causing others to undergo programmed cell death (apoptosis). Apoptosis is initiated at subinhibitory concentrations, suggesting that strategies to target this process may augment the benefits of antifungal agents.C aspofungin and other agents in the echinocandin class of antifungals have assumed an increasingly important role in the therapy of invasive candidiasis (1). These agents are nontoxic and exert potent fungicidal activity against Candida albicans and other Candida spp. Their antifungal activity is achieved through inhibition of (1,3)-␤-D-glucan synthase (2), an enzyme that synthesizes a major constituent of the fungal cell wall. Although the mechanism of activity for the echinocandins is known, the physiological mechanisms by which they cause cell death are not defined. At least two types of mammalian cell death, necrosis and apoptosis, have been described (3). Necrosis is death resulting from direct cellular injury, which is best defined by cell and organelle swelling and lysis (4). Apoptosis, on the other hand, is programmed cell death, the principal morphological feature of which is shrinkage of the cell and its nucleus (3, 4).Over the last decade, there have been a number of reports on apoptosis in yeas...

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Silver nanoparticles induce apoptotic cell death in Candida albicans through the increase of hydroxyl radicals

Cited by 210 publications

References 48 publications

Photodynamic ability of silver nanoparticles in inducing cytotoxic effects in breast and lung cancer cell lines

Photodynamic ability of silver nanoparticles in inducing cytotoxic effects in breast and lung cancer cell lines

Hyperthermia Sensitizes Rhizopus oryzae to Posaconazole and Itraconazole Action through Apoptosis

Caspofungin Kills Candida albicans by Causing both Cellular Apoptosis and Necrosis

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