Topic
Protoporphyrin IX
About: Protoporphyrin IX is a research topic. Over the lifetime, 2250 publications have been published within this topic receiving 65544 citations. The topic is also known as: PpIX.
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TL;DR: Testing a known inducer of cellular differentiation, methotrexate (MTX), in combination with ALA-PDT in LNCaP cells suggests that MTX, when used to modulate intracellular production of endogenous PpIX, may provide a new combination PDT approach for certain cancers.
Abstract: Photodynamic therapy (PDT) using 5-aminolaevulinic acid (ALA) to drive production of an intracellular photosensitiser, protoporphyrin IX (PpIX), is a promising cancer treatment. However, ALA-PDT is still suboptimal for thick or refractory tumours. Searching for new approaches, we tested a known inducer of cellular differentiation, methotrexate (MTX), in combination with ALA-PDT in LNCaP cells. Methotrexate alone promoted growth arrest, differentiation, and apoptosis. Methotrexate pretreatment (1 mg l−1, 72 h) followed by ALA (0.3 mM, 4 h) resulted in a three-fold increase in intracellular PpIX, by biochemical and confocal analyses. After exposure to 512 nm light, killing was significantly enhanced in MTX-preconditioned cells. The reverse order of treatments, ALA-PDT followed by MTX, yielded no enhancement. Methotrexate caused a similar relative increase in PpIX, whether cells were incubated with ALA, methyl-ALA, or hexyl-ALA, arguing against a major effect upon ALA transport. Searching for an effect among porphyrin synthetic enzymes, we found that coproporphyrinogen oxidase (CPO) was increased three-fold by MTX at the mRNA and protein levels. Transfection of LNCaP cells with a CPO-expressing vector stimulated the accumulation of PpIX. Our data suggest that MTX, when used to modulate intracellular production of endogenous PpIX, may provide a new combination PDT approach for certain cancers.
112 citations
TL;DR: Plant tissue homogenized in isotonic buffer was subjected to subcellular fractionation to prepare mitochondria and plastids essentially free of contamination by other cellular organelles, as determined by marker enzymes.
Abstract: The subcellular location of two enzymes in the biosynthetic pathway for protoporphyrin IX, coproporphyrinogen (coprogen) oxidase (EC 1.3.3.3) and protoporphyrinogen (protogen) oxidase (EC 1.3.3.4) has been investigated in etiolated pea (Pisum sativum) leaves and spadices of cuckoo-pint (Arum maculatum). Plant tissue homogenized in isotonic buffer was subjected to subcellular fractionation to prepare mitochondria and plastids essentially free of contamination by other cellular organelles, as determined by marker enzymes. Protogen oxidase activity measured fluorimetrically was reproducibly found in both mitochondria and etioplasts. In contrast, coprogen oxidase could be detected only in etioplasts, using either a coupled fluorimetric assay or a sensitive radiochemical method. The implications of these results for the synthesis of mitochondrial haem in plants is discussed.
112 citations
TL;DR: TPA-induced MMP-9 gene expression, tumor invasion, and colony formation were significantly reduced in MCF-7/HO-1 cells, compared with those in Neo-transfected cells, because of the beneficial role of HO-1 in blocking tumor invasion.
Abstract: In the present study, we investigated the antitumor effects of the invasiveness and migration of heme oxygenase 1 (HO-1) in human breast carcinoma cells. 12- O -tetradecanoylphorbol-13-acetate (TPA)–induced matrix metalloproteinase-9 (MMP-9) enzyme activity and gene expression at both protein and mRNA levels were examined in human breast carcinoma cells (MCF-7 and MDA-MB-231), and the addition of the MMP-9 inhibitor, SB3CT, significantly suppressed TPA-induced invasion and migration according to the in vitro Transwell assay. Elevation of HO-1 gene expression by ferric protoporphyrin IX inhibited TPA-induced invasion of MCF-7 cells, which was blocked by adding the heme oxygenase inhibitor, tin protoporphyrin IX, or transfection of cells with HO-1 short hairpin RNA. MCF-7 cells overexpressing HO-1 (MCF-7/HO-1) were established in the present study, and TPA-induced MMP-9 gene expression, tumor invasion, and colony formation were significantly reduced in MCF-7/HO-1 cells, compared with those in Neo-transfected cells. Activation of protein kinase Cα/extracellular signal-regulated kinases/AP-1 with stimulation of reactive oxygen species production was involved in TPA-induced invasion of MCF-7 cells, which was attenuated by HO-1 protein induced by ferric protoporphyrin IX or transfection of HO-1 expression vectors. Additionally, the addition of carbon monoxide, but not ferric ions, biliverdin, or bilirubin, inhibited TPA-induced invasion through suppressing MMP-9, extracellular signal-regulated kinases, and AP-1 activation stimulated by TPA. The beneficial role of HO-1 in blocking tumor invasion was first identified in this study. [Mol Cancer Ther 2008;7(5):1195–1206]
111 citations
TL;DR: ALA-IPL are beneficial in the management of acne vulgaris and may be used in combination with other forms of acne treatment or may be an alternative treatment for patients who do not want to take systemic retinoids.
Abstract: BackgroundPhotodynamic therapy (PDT) involves the activation of a photosensitizing agent by light to produce oxygen intermediates that destroy target tissues. Topical 5-aminolevulinic acid (ALA) is converted to protoporphyrin IX, a very potent photosensitizer, which accumulates in human skin, partic
110 citations
TL;DR: It is concluded that the high variability in eggshell pigment content is likely to reflect physiological influences (e.g. order of egg laying and the whole condition of the nesting female) rather than environmental interferences.
Abstract: Eggshell pigment constituents were determined by a high-performance liquid chromatography method. Most of the work was done on whole clutches of red-backed shrike ( Lanius collurio ). In addition to the known pigments (protoporphyrin IX, biliverdin), a new pigment, zinc-containing protoporphyrin IX, was found as well. Its content was highly variable—from 0% to 100%. The content of total protoporphyrin IX (with and without zinc) ranged from 1.72 to 114.84 nmol (average for whole clutches was 39.93 nmol), while the content of zinc-deficient protoporphyrin IX was ND (not detectable) -110.46 nmol (average for whole clutches was 34.02 nmol) and the content of zinc-containing protoporphyrin IX was ND - 32.28 nmol (average for whole clutches was 5.91 nmol). Zinc-containing protoporphyrin IX was absent in 33% of eggs, while zinc-deficient protoporphyrin IX was absent in a single case only (2%). If clutches from relatively “polluted” and “unpolluted” regions were compared, no differences have been found. Based on these findings is the conclusion that the high variability in eggshell pigment content is likely to reflect physiological influences (e.g. order of egg laying and the whole condition of the nesting female) rather than environmental interferences. This conclusion is in agreement with our previous findings. Additional data regarding the pigment content of seven other bird species are also included.
109 citations