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Métodos Terapéuticos y Terapias MTCI
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1.
Planta Med ; 68(11): 1042-4, 2002 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-12451500

RESUMEN

Purification of a cytotoxic crude alkaloid extract of Cassytha filiformis led to the isolation of four known aporphine alkaloids: neolitsine, dicentrine, cassythine (= cassyfiline) and actinodaphnine. Their structures were determined by analysis of spectroscopic data. All isolated alkaloids were tested for their cytotoxic activities on cancer and non-cancer cell lines in vitro. Neolitsine was the most active against HeLa and 3T3 cells (IC 50 :21.6 microM, and 21.4 microM, respectively). Cassythine and actinodaphnine showed the highest activity against Mel-5 (IC 50 : 24.3 microM and 25.7 microM, respectively) and HL-60 (IC 50 : 19.9 microM and 15.4 microM, respectively). This is the first report on the cytotoxic activity of C. filiformis extract and of neolitsine and cassythine. Furthermore, the complete NMR data of cassythine and actinodaphnine are given here for the first time.


Asunto(s)
Aporfinas/farmacología , Lauraceae , Fitoterapia , Extractos Vegetales/farmacología , Células 3T3/efectos de los fármacos , Animales , Aporfinas/química , Femenino , Células HL-60/efectos de los fármacos , Células HeLa/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Espectroscopía de Resonancia Magnética , Ratones , Extractos Vegetales/química , Células Tumorales Cultivadas/efectos de los fármacos
2.
Planta Med ; 68(7): 647-9, 2002 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12143003

RESUMEN

The dichloromethane extract of leaves of Croton zambesicus (Euphorbiaceae) showing in vitro cytotoxicity against human cervix carcinoma cells was investigated in order to identify its active compounds. A bio-guided fractionation by HSCCC followed by MPLC led us to isolate a trachylobane diterpene, ent-trachyloban-3beta-ol, with cytotoxic properties (IC50 on HeLa cells = 7.3 microg/ml). This is the first report on the cytotoxicity of a trachylobane diterpene.


Asunto(s)
Antineoplásicos/farmacología , Croton/química , Diterpenos/farmacología , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Diterpenos/química , Diterpenos/aislamiento & purificación , Ensayos de Selección de Medicamentos Antitumorales , Células HeLa , Humanos , Concentración 50 Inhibidora
3.
Anticancer Drug Des ; 15(3): 191-201, 2000 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-11049087

RESUMEN

Cryptolepine and neocryptolepine are two indoloquinoline alkaloids isolated from the roots of the African plant Cryptolepis sanguinolenta. Both drugs have revealed antibacterial and antiparasitic activities and are strongly cytotoxic to tumour cells. We have recently shown that cryptolepine can intercalate into DNA and stimulates DNA cleavage by human topoisomerase II. In this study, we have investigated the mechanism of action and cytotoxicity of neocryptolepine, which differs from the parent isomer only by the orientation of the indole unit with respect to the quinoline moiety. The biochemical and physicochemical results presented here indicate that neocryptolepine also intercalates into DNA, preferentially at GC-rich sequences, but exhibits a reduced affinity for DNA compared with cryptolepine. The two alkaloids interfere with the catalytic activity of human topoisomerase II but the poisoning activity is slightly more pronounced with cryptolepine than with its isomer. The data provide a molecular basis to account for the reduced cytotoxicity of neocryptolepine compared with the parent drug.


Asunto(s)
Alcaloides/toxicidad , Antineoplásicos Fitogénicos/toxicidad , Indoles , Sustancias Intercalantes/toxicidad , Quinolinas , Inhibidores de Topoisomerasa II , Alcaloides/metabolismo , Animales , Antineoplásicos Fitogénicos/metabolismo , Bovinos , Dicroismo Circular , ADN/efectos de los fármacos , ADN/metabolismo , Daño del ADN , Huella de ADN , ADN-Topoisomerasas de Tipo II/metabolismo , Humanos , Alcaloides Indólicos , Sustancias Intercalantes/metabolismo , Células KB , Melanoma Experimental/tratamiento farmacológico , Ratones , Ratones Endogámicos , Raíces de Plantas/química , Plantas Medicinales/química , Especificidad por Sustrato
4.
Biochemistry ; 38(24): 7719-26, 1999 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-10387011

RESUMEN

Cryptolepine, matadine, and serpentine are three indoloquinoline alkaloids isolated from the roots of African plants: Cryptolepis sanguinolenta, Strychnos gossweileri, and Rauwolfia serpentina, respectively. For a long time, these alkaloids have been used in African folk medicine in the form of plant extracts for the treatment of multiple diseases, in particular as antimalarial drugs. To date, the molecular basis for their diverse biological effects remains poorly understood. To elucidate their mechanism of action, we studied their interaction with DNA and their effects on topoisomerase II. The strength and mode of binding to DNA of the three alkaloids were investigated by spectroscopy. The alkaloids bind tightly to DNA and behave as typical intercalating agents. All three compounds stabilize the topoisomerase II-DNA covalent complex and stimulate the cutting of DNA by topoisomerase II. The poisoning effect is more pronounced with cryptolepine than with matadine and serpentine, but none of the drugs exhibit a preference for cutting at a specific base. Cryptolepine which binds 10-fold more tightly to DNA than the two related alkaloids proves to be much more cytotoxic toward B16 melanoma cells than matadine and serpentine. The cellular consequences of the inhibition of topoisomerase II by cryptolepine were investigated using the HL60 leukemia cell line. The flow cytometry analysis shows that the drug alters the cell cycle distribution, but no sign of drug-induced apoptosis was detected when evaluating the internucleosomal fragmentation of DNA in cells. Cryptolepine-treated cells probably die via necrosis rather than via apoptosis. The results provide evidence that DNA and topoisomerase II are the primary targets of cryptolepine, matadine, and serpentine.


Asunto(s)
Alcaloides/farmacología , ADN-Topoisomerasas de Tipo II/química , ADN/química , ADN/efectos de los fármacos , Indoles , Sustancias Intercalantes/farmacología , Quinolinas , Alcaloides/química , Alcaloides/metabolismo , Antineoplásicos Fitogénicos/farmacología , Sitios de Unión/efectos de los fármacos , Muerte Celular/efectos de los fármacos , ADN/metabolismo , ADN-Topoisomerasas de Tipo II/metabolismo , Electroquímica , Inhibidores Enzimáticos/farmacología , Polarización de Fluorescencia , Células HL-60 , Humanos , Alcaloides Indólicos , Sustancias Intercalantes/química , Sustancias Intercalantes/metabolismo , Alcaloides de Triptamina Secologanina/química , Alcaloides de Triptamina Secologanina/metabolismo , Alcaloides de Triptamina Secologanina/farmacología , Análisis Espectral , Inhibidores de Topoisomerasa II
5.
Planta Med ; 60(1): 45-9, 1994 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-8134416

RESUMEN

In this work, we have analysed the effects of alpha-hederin, a monodesmosidic triterpenoid saponin isolated from Hedera helix, on mouse B16 melanoma cells and non-cancer mouse 3T3 fibroblasts cultured in vitro. Our results indicate that, in a serum-free medium, alpha-hederin is cytotoxic and inhibits proliferation in both cell lines at rather low concentrations (< 5 micrograms/ml) after only 8 hours of treatment. Its cytotoxicity decreases in the presence of serum in which BSA seems to be able to bind the saponin. alpha-Hederin also induces vacuolization of the cytoplasm and membrane alterations leading to cell death.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Ácido Oleanólico/análogos & derivados , Plantas/química , Saponinas/farmacología , Células 3T3 , Animales , Antineoplásicos Fitogénicos/aislamiento & purificación , Secuencia de Carbohidratos , Ratones , Datos de Secuencia Molecular , Estructura Molecular , Saponinas/aislamiento & purificación , Células Tumorales Cultivadas
6.
Arch Toxicol ; 68(4): 246-54, 1994.
Artículo en Inglés | MEDLINE | ID: mdl-8067897

RESUMEN

The effects of selenium compounds such as sodium selenite, sodium selenate, seleno-DL-cystine and seleno-DL-methionine (100 microM and 10 microM) on B16 and pigmented cloned pB16 murine melanoma cells were investigated in vitro. At the tested concentrations, B16 cells showed a greater sensitivity to the toxic effects of sodium selenite and seleno-DL-cystine than pB16 cells, whereas no decrease of B16 and pB16 cell number was observed after incubation with sodium selenate or seleno-DL-methionine. Glutathione (GSH) percentages were strongly decreased only by selenite and seleno-DL-cystine; it was marked more in B16 than in pB16 cells. The pretreatment of B16 cells with a GSH depleting agent (10 microM buthionine-[S,R]-sulfoximine) did not significantly influence the cytotoxic effects of selenite and seleno-DL-cystine. On both cell populations, GSH preincubation (50 microM) enhanced the cytotoxicity of selenite whereas the survival of seleno-DL-cystine treated cells was increased. Glutathione peroxidase (GSH-Px) activity in B16 cells was more sensitive than in pB16 cells to the activating effect of selenite, and particularly of seleno-DL-cystine: however, cell-free controls indicated that activation was mainly due to glutathione reductase. The rate of 75Se (as sodium selenite) uptake in both cell populations was maximal within the first hour of incubation, with a preferential accumulation in the cytosol; after 24 h of incubation, the amount of 75Se in cytosol and pellet was approximately the same.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Melanoma Experimental/patología , Selenio/farmacología , Animales , División Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Clonales , Glutatión/efectos de los fármacos , Glutatión Peroxidasa/efectos de los fármacos , Melanoma Experimental/metabolismo , Ratones , Ratones Endogámicos C57BL , Pigmentación , Radioisótopos de Selenio/metabolismo , Células Tumorales Cultivadas
7.
Anticancer Res ; 10(4): 1029-33, 1990.
Artículo en Inglés | MEDLINE | ID: mdl-2382974

RESUMEN

The effects exerted by FeSO4, in the presence or absence of vitamin C, on melanogenesis and proliferation in mouse B16 melanoma cells in culture were analysed either in serum-free (MEM-N2) or in serum-supplemented media. These cellular parameters can be either stimulated or on the contrary inhibited, depending on the metal concentration, the presence or the absence of vitamin C and serum, and on the type of culture (subconfluent or clonal). Vitamin C toxicity for B16 cells was decreased in the presence of FeSO4.


Asunto(s)
Compuestos Ferrosos/farmacología , Melanoma Experimental/patología , Animales , Ácido Ascórbico/farmacología , Diferenciación Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Precipitación Química , Medios de Cultivo , Compuestos Ferrosos/metabolismo , Melaninas/análisis , Ratones , Ratones Endogámicos C57BL
8.
Anticancer Res ; 10(2A): 391-5, 1990.
Artículo en Inglés | MEDLINE | ID: mdl-2346313

RESUMEN

The effects exerted by CuSO4, in the presence or absence of vitamin C, on melanogenesis and proliferation in mouse B16 melanoma cells in culture were analysed either in serum-free (MEM-N2) or in serum-supplemented media. The stimulation or the inhibition of these cellular parameters can be induced, depending on the metal concentration, the presence or absence of vitamin C, the composition of the culture medium and on the type of culture (subconfluent or clonal). Vitamin C toxicity for B16 cells was generally increased in serum-free medium, in clonal cultures, or in the presence of CuSO4.


Asunto(s)
Ácido Ascórbico/farmacología , Cobre/farmacología , Melanoma Experimental/patología , Diferenciación Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Cobre/metabolismo , Sulfato de Cobre , Medios de Cultivo , Humanos , Melanoma Experimental/metabolismo , Ensayo de Tumor de Célula Madre
10.
J Ethnopharmacol ; 15(3): 305-16, 1986 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-3724211

RESUMEN

The potential cytotoxic activities of 46 alkaloids isolated from different Strychnos species were tested on different cancer or normal cells cultured in vitro. The authors used a relatively simple microtest which gives good reproducibility. Most of the active compounds belong to the usambarane skeleton but other structure-activity relationships are being discussed.


Asunto(s)
Alcaloides/farmacología , Antineoplásicos Fitogénicos , Antineoplásicos , División Celular/efectos de los fármacos , Alcaloides/toxicidad , Animales , Antineoplásicos/toxicidad , Células Cultivadas , Fenómenos Químicos , Química , Evaluación Preclínica de Medicamentos , Humanos , Ratones , Ratones Endogámicos , Neoplasias Experimentales/patología , Relación Estructura-Actividad
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