α‐Tomatine, the major saponin in tomato, induces programmed cell death mediated by reactive oxygen species in the fungal pathogen <i>Fusarium oxysporum</i>

Ito, Shin; Ihara, Takashi; Tamura, Hiro Omi; Tanaka, Shuhei; Ikeda, Tsuyoshi; Kajihara, Hiroshi; Dissanayake, Chandrika; Abdel-Motaal, Fatma F.; El‐Sayed, Magdi A.

doi:10.1016/j.febslet.2007.06.010

Cited by 114 publications

(82 citation statements)

References 33 publications

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“…Recently, Ito et al [1] found that the antibiotic effect of tomatine against the fungal pathogen Fusarium oxysporum involves activation of phosphotyrosine kinase and G-protein signaling pathways leading to Ca 2+ elevation and accumulation of reactive-oxygen species (ROS). In related studies, Simons et al [2] found that the mode of action of atomatine towards yeast cells involving cell membrane permeilization is distinct from that of the aglycone tomatidine that lacks the tetrasaccharide side chain.…”

Section: Introductionmentioning

confidence: 99%

Protective effect of dietary tomatine against dibenzo[a,l]pyrene (DBP)‐induced liver and stomach tumors in rainbow trout

Friedman¹,

McQuistan²,

Hendricks³

et al. 2007

Molecular Nutrition Food Res

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The potential anti-carcinogenic effects of tomatine, a mixture of commercial tomato glycoalkaloids alpha-tomatine and dehydrotomatine (10:1), were examined in the rainbow trout chemoprevention model. Prior to the chemoprevention study, a preliminary toxicity study revealed that tomatine in the diet fed daily at doses from 100 to 2000 parts per million (ppm) for 4 weeks was not toxic to trout. For the tumor study, replicate groups of 105 trout were fed diets containing dibenzo[a,l]pyrene (DBP) alone (224 ppm), (N = 3), DBP plus tomatine at 2000 ppm (N = 2), tomatine alone (N = 2), or control diet (N = 2) for 4 weeks. The fish were then returned to control diet for 8 months and necropsied for histopathology. Dietary tomatine was found to reduce DBP-initiated liver tumor incidence from 37.0 to 19.0% and stomach tumor incidence from 46.4 to 29.4%. Tomatine also reduced stomach tumor multiplicity. The tomatine-containing diets did not induce mortality, change in fish weights, or liver weights. No adverse pathological effects in the tissues of the fish on the tomatine diets were observed. Dose-response and chemopreventive mechanisms for tomatine protection remain to be examined. This is the first report on the anticarcinogenic effects of tomatine in vivo.

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Section: Introductionmentioning

confidence: 99%

Protective effect of dietary tomatine against dibenzo[a,l]pyrene (DBP)‐induced liver and stomach tumors in rainbow trout

Friedman¹,

McQuistan²,

Hendricks³

et al. 2007

Molecular Nutrition Food Res

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“…Apoptosis has been observed in a number of filamentous fungi, such as Aspergillus nidulans, Aspergillus fumigatus, Neurospora crassa, and Fusarium oxysporum (12)(13)(14)(15). Various physiological stresses, ionizing radiation, and hyperthermia have been reported to trigger apoptosis in fungi and cancer cells (14)(15)(16).…”

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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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“…It is interesting that in F. oxysporum f. sp. lycopersici, the observed sensitivity to ␣-tomatine is a result of ␣-tomatine-induced programmed cell death in the fungus rather than an effect on membranes (23). Furthermore, the ␣-tomatine aglycone tomatidine inhibits sterol biosynthesis in Saccharomyces cerevisiae (50), indicating that the biological properties of saponins and their degradation products are complex.…”

Section: Discussionmentioning

confidence: 97%

Streptomyces scabies87-22 Possesses a Functional Tomatinase

Seipke

Loria

2008

J Bacteriol

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The actinomycete Streptomyces scabies 87-22 is the causal agent of common scab, an economically important disease of potato and taproot crops. Sequencing of the S. scabies 87-22 genome revealed the presence of a gene with high homology to the gene encoding the ␣-tomatine-detoxifying enzyme tomatinase found in fungal tomato pathogens. The tomA gene from S. scabies 87-22 was cotranscribed with a putative family 1 glycosyl hydrolase gene, and purified TomA protein was active only on ␣-tomatine and not potato glycoalkaloids or xylans. Tomatinase-null mutants were more sensitive to ␣-tomatine than the wild-type strain in a disk diffusion assay. Interestingly, tomatine affected only aerial mycelium and not vegetative mycelium, suggesting that the target(s) of ␣-tomatine is not present during vegetative growth. Severities of disease for tomato seedlings affected by S. scabies 87-22 wild-type and ⌬tomA1 strains were indistinguishable, suggesting that tomatinase is not important in pathogenicity on tomato plants. However, conservation of tomA on a pathogenicity island in S. acidiscabies and S. turgidiscabies suggests a role in plant-microbe interaction.

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α‐Tomatine, the major saponin in tomato, induces programmed cell death mediated by reactive oxygen species in the fungal pathogen Fusarium oxysporum

Cited by 114 publications

References 33 publications

Protective effect of dietary tomatine against dibenzo[a,l]pyrene (DBP)‐induced liver and stomach tumors in rainbow trout

Protective effect of dietary tomatine against dibenzo[a,l]pyrene (DBP)‐induced liver and stomach tumors in rainbow trout

Hyperthermia Sensitizes Rhizopus oryzae to Posaconazole and Itraconazole Action through Apoptosis

Streptomyces scabies87-22 Possesses a Functional Tomatinase

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