14 research outputs found
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Effect of ultraviolet B induced oxidative stress in conjugation with copper on human melanocytes and melanosomal properties
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Effect of ultraviolet B induced oxidative stress in conjugation with copper on human melanocytes and melanosomal properties
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Pro-Oxidant Properties of Melanosomal Melanin from Melanoma Origin
Melanoma cells, in comparison to normal melanocytes, contain
higher concentrations of redox active species and yet are
inefficient in mediating oxidative stress. We attribute these
features to changes of intracellular melanosomes and melanin
reactivity during the pathogenic process. Eumelanins are redox
active pigments containing hydroquinone, semiquinone, quinone
and quinone-imine functionalities within their structure. We have
previously shown that pro-oxidant properties of synthetic melanin
are enhanced by stabilization of the oxidized form of melanin as a
result of metal chelation. Chemical studies using DNA clipping
activity of isolated melanosomes from different sources indicated
enhanced pro-oxidant properties of melanosomes from melanoma
origin compared to melanin from normal melanocytes and sepia
origin. Electron paramagnetic resonance spin trapping studies
confirm these results both in electrochemically polymerized
dihydroquinones and in intact human melanoma cells and
suggested generation of superoxide and hydroxyl radicals.
Ultrastructural investigations of melanosomes by electron
microscopy revealed abnormalities in melanin deposition and
membrane of the melanoma melanosomes compared to
melanocyte melanosomes, which may play a part in higher
reactivity of melanoma melanosomes. in related experiments
exposure of normal human melanocytes to ultraviolet light
radiation –B plus copper and cadmium (but not zinc) salts led to
cells that phenotypically resembled dysplastic nevus cells in
culture
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Pro-Oxidant Properties of Melanosomal Melanin from Melanoma Origin
Melanoma cells, in comparison to normal melanocytes, contain
higher concentrations of redox active species and yet are
inefficient in mediating oxidative stress. We attribute these
features to changes of intracellular melanosomes and melanin
reactivity during the pathogenic process. Eumelanins are redox
active pigments containing hydroquinone, semiquinone, quinone
and quinone-imine functionalities within their structure. We have
previously shown that pro-oxidant properties of synthetic melanin
are enhanced by stabilization of the oxidized form of melanin as a
result of metal chelation. Chemical studies using DNA clipping
activity of isolated melanosomes from different sources indicated
enhanced pro-oxidant properties of melanosomes from melanoma
origin compared to melanin from normal melanocytes and sepia
origin. Electron paramagnetic resonance spin trapping studies
confirm these results both in electrochemically polymerized
dihydroquinones and in intact human melanoma cells and
suggested generation of superoxide and hydroxyl radicals.
Ultrastructural investigations of melanosomes by electron
microscopy revealed abnormalities in melanin deposition and
membrane of the melanoma melanosomes compared to
melanocyte melanosomes, which may play a part in higher
reactivity of melanoma melanosomes. in related experiments
exposure of normal human melanocytes to ultraviolet light
radiation –B plus copper and cadmium (but not zinc) salts led to
cells that phenotypically resembled dysplastic nevus cells in
culture
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Melanin as a target for melanoma chemotherapy: Pro-oxidant effect of oxygen and metals on melanoma viability
Melanoma cells have a poor ability to mediate oxidative stress, which may be attributed to constitutive abnormalities in their melanosomes. We hypothesize that disorganization of the melanosomes will allow chemical targeting of the melanin within. Chemical studies show that under oxidative conditions, synthetic melanins demonstrate increased metal affinity and a susceptibility to redox cycling with oxygen to form reactive oxygen species. The electron paramagnetic resonance (EPR)-active 5,5'-dimethyl-pyrollidine N-oxide spin adduct was used to show that binding of divalent Zn or Cu to melanin induces a pro-oxidant response under oxygen, generating superoxide and hydroxyl radicals. A similar pro-oxidant behaviour is seen in melanoma cell lines under external peroxide stress. Melanoma cultures grown under 95% O-2/5% CO2 atmospheres show markedly reduced viability as compared with normal melanocytes. Cu- and Zn-dithiocarbamate complexes, which induce passive uptake of the metal ions into cells, show significant antimelanoma activity. The antimelanoma effect of metal- and oxygen-induced stress appears additive rather than synergistic; both treatments are shown to be significantly less toxic to melanocytes