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1.
Phytomedicine ; 14(11): 739-46, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17482444

RESUMO

Betalains are water-soluble nitrogenous vacuolar pigments present in flowers and fruits of many caryophyllales with potent antioxidant properties. In the present study the antiproliferative effects of betanin, a principle betacyanin pigment, isolated from the fruits of Opuntia ficus-indica, was evaluated on human chronic myeloid leukemia cell line (K562). The results show dose and time dependent decrease in the proliferation of K562 cells treated with betanin with an IC(50) of 40 microM. Further studies involving scanning and transmission electron microscopy revealed the apoptotic characteristics such as chromatin condensation, cell shrinkage and membrane blebbing. Agarose electrophoresis of genomic DNA of cells treated with betanin showed fragmentation pattern typical for apoptotic cells. Flow cytometric analysis of cells treated with 40 microM betanin showed 28.4% of cells in sub G0/G1 phase. Betanin treatment to the cells also induced the release of cytochrome c into the cytosol, poly (ADP) ribose polymerase (PARP) cleavage, down regulation Bcl-2, and reduction in the membrane potentials. Confocal microscopic studies on the cells treated with betanin suggest the entry of betanin into the cells. These studies thus demonstrate that betanin induces apoptosis in K562 cells through the intrinsic pathway and is mediated by the release of cytochrome c from mitochondria into the cytosol, and PARP cleavage. The antiproliferative effects of betanin add further value to the nutritional characteristics of the fruits of O. ficus-indica.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Betacianinas/farmacologia , Proliferação de Células/efeitos dos fármacos , Opuntia , Fitoterapia , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/uso terapêutico , Betacianinas/administração & dosagem , Betacianinas/uso terapêutico , Ciclo Celular/efeitos dos fármacos , Corantes/administração & dosagem , Corantes/farmacologia , Corantes/uso terapêutico , Frutas , Humanos , Concentração Inibidora 50 , Células K562/efeitos dos fármacos , Células K562/ultraestrutura , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
2.
Neoplasma ; 52(3): 225-30, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15875084

RESUMO

Oridonin, an extract from the Chinese herb Rabdosia rubescens, is currently one of the most important traditional Chinese herbal medicines. Recently oridonin has been reported to have anti- tumor effects in a large variety of malignant diseases. In this study, we investigated the apoptotic inducing effect of oridonin in leukemia K562 cells and its mechanism. Cell growth inhibition was measured using a microculture tetrazolium assay, apoptosis was measured by flow cytometry and electron microscopy as well as by DNA fragmentation analysis. Telomerase activity was measured by TRAP-enzyme- linked immunosorbent assay, and the expression of Bcl-2 and Bax proteins was detected by western blot analysis. The results showed that oridonin could inhibit the proliferation and induce apoptosis on leukemia K562 cells remarkably. Telomerase activity as well as Bcl-2 expression was down- regulated, while Bax expression was up-regulated concurrently, when apoptosis ocurred. We therefore conclude that oridonin demonstrated anti-proliferative and apoptosis-inducing effects on K562 cells in vitro, and that changes in bcl-2 and bax protein levels as well as telomerase activity may play an important role in its mechanism of action.


Assuntos
Antineoplásicos/farmacologia , Apoptose , Diterpenos/farmacologia , Células K562/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fragmentação do DNA , Diterpenos/química , Diterpenos do Tipo Caurano , Humanos , Células K562/ultraestrutura , Microscopia Eletrônica , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Telomerase/antagonistas & inibidores , Telomerase/metabolismo , Proteína X Associada a bcl-2
3.
Br J Cancer ; 83(1): 69-73, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10883670

RESUMO

The carcinogenicity of the vegetative tissues of bracken fern (Pteridium) has long been established. More recently, the carcinogenic effects of the spores of bracken have also been recognized. Both vegetative tissues and spores of bracken can induce adducts in DNA in animal tissues, but the possible genotoxic or carcinogenic effects of spores from fern species other than bracken are unknown. The single-cell gel electrophoresis ('comet') assay was used to investigate whether fern spores can cause DNA damage in vitro. Extracts of spores from six fern species were administered to cultured human premyeloid leukaemia (K562) cells. Spore extracts of five fern species: Anemia phyllitidis, Dicksonia antarctica, Pteridium aquilinum, Pteris vittata and Sadleria pallida, induced significantly more DNA strand breaks than those in the control groups. Only in one species, Osmunda regalis, was the effect no different from that in the control groups. Using extracts from A. phyllitidis and P. vittata, the extent of DNA damage was increased by increasing the original dose 10 times, whereas an experiment in which exposure times were varied suggested that the highest levels of strand breaks appear after 2 h exposure. Simultaneous incubation with human S9 liver enzyme mix ablated the damaging effect of the extracts. Our data show that fern spore extracts can cause DNA damage in human cells in vitro. Considering the strong correlation between DNA damage and carcinogenic events, the observations made in this report may well have some implications for human health.


Assuntos
Dano ao DNA , DNA/efeitos dos fármacos , Mutagênicos/toxicidade , Extratos Vegetais/toxicidade , Ensaio Cometa , DNA de Neoplasias/efeitos dos fármacos , Humanos , Processamento de Imagem Assistida por Computador , Inativação Metabólica , Células K562/efeitos dos fármacos , Células K562/ultraestrutura , Microssomos Hepáticos/enzimologia , Mutagênicos/isolamento & purificação , Fenômenos Fisiológicos Vegetais , Especificidade da Espécie , Esporos/química
4.
Hunan Yi Ke Da Xue Xue Bao ; 25(5): 480-2, 2000 Oct 28.
Artigo em Chinês | MEDLINE | ID: mdl-12212126

RESUMO

UNLABELLED: The effects of Chinese medicine jiexinkang(JXK) on apoptosis of leukemic cells were studied by morphology approach and electrophoresis of DNA fragments. RESULTS: 1. The apoptotic cells and apoptotic bodies were found by electrical microscopy and the typical ladders of DNA fragments were detected by electrophoresis. 2. JXK induced apoptosis of leukemic cells(HL-60 and K562) in a certain range of concentration and at appropriate time. The time to K562 cell apoptosis was longer than that of HL-60 and its dosage was larger than that of HL-60. CONCLUSION: HL-60 and K562 leukemic cell apoptosis may be induced by JXK and there is correlation between dose and time. The study provides experimental evidences for the clinical treatment of leukemia.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Fragmentação do DNA , DNA de Neoplasias/análise , Combinação de Medicamentos , Células HL-60/ultraestrutura , Humanos , Células K562/ultraestrutura
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