RESUMEN
Plumbagin is a naphthoquinone found in the roots of Plumbago zeylanica. Here, we report an investigation to evaluate its antiobesity activity. The preliminary binding affinity of plumbagin to human pancreatic lipase (PL) was determined using molecular docking simulation. The in vitro PL inhibitory potential and the kinetics of inhibition were studied to validate and confirm the results obtained from molecular docking. The IC50 for PL was found to be 82.08 ± 9.47 µM, and the kinetics of inhibition was found to be of the mixed type. Further, the in vivo evaluation revealed that rats treated with plumbagin 1 mg/kg showed significant decrease in serum triglycerides (TG) and area under the curve of serum TG when compared with vehicle-treated rats. It was also seen that plumbagin possessed significant antiadipogenic effect as demonstrated by reduced oil red O staining and decreased TG contents. Thus, we conclude that plumbagin is a promising molecule to combat obesity and further optimization of plumbagin to yield plumbagin analogues will result in its improved activity profile.
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Adipocitos/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Lipasa/antagonistas & inhibidores , Naftoquinonas/farmacología , Obesidad/tratamiento farmacológico , Células 3T3-L1 , Adipocitos/citología , Animales , Humanos , Cinética , Lipasa/metabolismo , Masculino , Ratones , Simulación del Acoplamiento Molecular , Raíces de Plantas/química , Plumbaginaceae/química , Ratas , Ratas Wistar , Triglicéridos/sangreRESUMEN
BACKGROUND: The anti-cancer activity of phytomolecules present in turmeric or haridra (Curcuma longa Linn) extracts against cancer has been described in various 'in vitro and in vivo' studies. OBJECTIVE: In the present study, in vitro and in vivo anti-cancer and chemo-preventive activity of a new standardized Supercritical Turmeric Oil Extract (SCTOE) NBFR-03 was evaluated in cervical cancer models. METHODS AND MATERIALS: In vitro cytotoxicity of this formulation was assessed at 10, 20, 40, and 80 µg/ml concentrations, in three cervical cancer cell lines (HeLa, SiHa, ME180) using Sulforhodamine B assay. The in vivo anti-cancer activity was evaluated in two groups of female nude mice; the first one was with tumor xenograft implants and at the same time treatment was started with 96 µl/kg/day p.o. and 192 µl/kg/day p.o. NBFR-03 for three months. The second group was kept as chemoprevention group where mice were pre-treated with the formulation (96 µl/kg/day p.o.) for two weeks and injected with cancer cell suspension with continued treatment for three months. RESULTS: No cytotoxicity was seen in any cell line with the extract when compared to positive control (Adriamycin 10 µg/ml). In mice the first treatment group with tumor xenograft implants did not show any significant anti-tumor activity but showed a trend where higher dose group had smaller tumor volumes as compared to lower dose group and controls (p = 0.37 and p = 0.34 respectively). The chemopreventive group with pre-treated mice also showed smaller tumor size as compared to controls (p = 0.163). CONCLUSION: NBFR-03 turmeric oil extract showed a promising trend in mice pre-treated with NBFR-03. There is a scope for further studying the potential of this extract as complementary therapy and as a chemopreventive.
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CONTEXT: Oral cancers represent a disparate group of tumors with diverse clinical behavior and chemosensitivity profile. Currently, it is difficult to predict whether a tumor will respond to chemotherapy and which drug(s) will achieve the maximum clinical response. AIMS: To study in vitro chemosensitivity profile of oral cancers and to correlate the in vitro chemosensitivity of oral cancer to clinical response to chemotherapy. SETTINGS AND DESIGN: Prospective study in a tertiary cancer care center. METHODS AND MATERIAL: We prospectively studied the chemosensitivity profile of 57 untreated, advanced, unresectable oral cancers to cisplatin, methotrexate, 5-fluorouracil and their combinations by using histoculture drug response assay (HDRA) and correlated them to the clinical response to chemotherapy. STATISTICAL ANALYSIS USED: Chi Square test. RESULTS: Biopsy samples were successfully histocultured in 52/57 (91%) cases. Of these 52 evaluable patients, 47 had primary gingivo-buccal cancers and five had tongue / floor of mouth cancers. Based on the assay, 27 (52%) tumors were sensitive to cisplatin, 27 (52%) to methotrexate, 24 (46%) to 5-fluorouracil, 38 (73%) to combination of cisplatin and methotrexate and 36 (69%) to combination of cisplatin and 5-fluorouracil. Of these, 31 patients with good performance status received two cycles of chemotherapy using one or more of these test drugs. There was a significant correlation (p=0.03) between the in vitro chemosensitivity and the clinical response. Negative predictive value of the test was 80%, positive predictive value-69%, sensitivity-79% and specificity -71%. The overall accuracy of the assay was 74%. CONCLUSIONS: We found HDRA to be a fairly good predictor of chemo-response of oral cancer.
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Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias de la Boca/tratamiento farmacológico , Antimetabolitos Antineoplásicos/farmacología , Antimetabolitos Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Bioensayo , Cisplatino/farmacología , Cisplatino/uso terapéutico , Femenino , Fluorouracilo/farmacología , Fluorouracilo/uso terapéutico , Humanos , Técnicas In Vitro , Masculino , Metotrexato/farmacología , Metotrexato/uso terapéutico , Persona de Mediana Edad , Estudios Prospectivos , Resultado del TratamientoRESUMEN
Immobilized callus cultures of Tinospora cordifolia (Willd) Miers ex Hooks and Thoms were investigated to find out the combined effect of elicitation, cell permeabilization with chitosan and in situ product recovery by polymeric neutral resin-like Diaion HP 20. In this study, callus cultures of T. cordifolia were immobilized using sodium alginate and calcium chloride and the beads were cultured in Murashige and Skoog's basal medium along with benzyl adenine (BA), 2,4-dichlorophenoxy acetic acid (2,4-D) and 3% sucrose. The immobilized cultures, when subjected to elicitation and cell permeabilization with chitosan and in situ removal of the secondary metabolites by addition of resin, showed a 10-fold increase in production of arabinogalactan (0.490% dry weight) as compared to respective controls devoid of resin and chitosan. This indicates that in situ adsorption may have reduced the feedback inhibition caused by accumulation of secondary metabolites in the media, while the dual effect of elicitation and cell permeabilization by chitosan may have released the intracellular (secreted) berberine and the polysaccharide arabinogalactan, respectively.
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Galactanos/biosíntesis , Tinospora/metabolismo , Adsorción , Berberina/aislamiento & purificación , Berberina/metabolismo , Biotecnología , Células Inmovilizadas , Galactanos/aislamiento & purificación , Concentración de Iones de Hidrógeno , Resinas de Intercambio Iónico , Cinética , PoliestirenosRESUMEN
Lonidamine (LNA) is antitumor agent that lacks the characteristic properties of antiproliferative drugs and has narrow spectrum of antitumour effects. It is also a hyperthermia sensitizer. Hyperthermia affects on various cellular organelles, and the malignant cells are known to be more sensitive to hyperthermia. The present study examines the in vitro effects of LNA (0.01 and 0.02 mM) and hyperthermia (42 degrees C for 1 and 2 hrs) alone and in combination, on 11 human chronic myeloid leukemia cell samples. The inhibition in incorporation of 3H-thymidine was statistically significant (P less than 0.001) in human CML cells when exposed to the combination of LNA (0.01 and 0.02 mM) with hyperthermia (1 and 2 hrs) compared to the single treatment either at the same concentration of LNA at 37 degrees C or hyperthermia alone. Cytotoxicity was evaluated as the inhibition of the incorporation of 3H-thymidine in the cellular nucleic acid. The drug effects were estimated from the changes in rates of incorporation of precursor into DNA and compared with untreated control samples. Cancer cells were incubated in vitro in the presence of radioactive 3H-thymidine and drug.
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Antineoplásicos/farmacología , ADN de Neoplasias/biosíntesis , Hipertermia Inducida , Indazoles/farmacología , Leucemia Mieloide/metabolismo , Pirazoles/farmacología , Células Cultivadas , Terapia Combinada , Humanos , Leucemia Mieloide/terapiaRESUMEN
Forty-seven ovarian cancer cases in which 20 were previously treated with cisplatin (cisPt) based chemotherapy, were checked for in vitro chemosensitivity using MTT assay. The drugs included in the study were cisPt, adriamycin (ADR), epirubicin (EPR) and etoposide (ETO). The logarithemic concentrations (0.1, 1.0, 10.0 and 100.0 micrograms/ml) of these drugs were used in the MTT assay. The IC50 values for these drugs in the above tumor samples were calculated. The effect of pretreatment with cisPt based chemotherapy on the emergence of drug resistance, expression of p53 protein (detected using immunohistochemical method by employing monoclonal antibody to p53) and intracellular glutathione (GSH) levels was also studied. Our results demonstrated the superiority of EPR in terms of its efficacy as compared to the other drugs used in the study. EPR was effective in both, previously cisPt-exposed and cisPt-unexposed ovarian cancer cases indicating its importance as a second line chemotherapy in the refractory ovarian carcinoma cases. Pre-exposure to cisPt based chemotherapy appears to result in the emergence of cisPt resistance, elevated intracellular GSH levels as well as p53 positivity. A statistically significant correlation was also observed between ADR and EPR resistance and p53 positivity (P < 0.01 and 0.05 respectively).
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Antineoplásicos/uso terapéutico , Cisplatino/uso terapéutico , Glutatión/metabolismo , Neoplasias Ováricas/tratamiento farmacológico , Proteína p53 Supresora de Tumor/metabolismo , Doxorrubicina/uso terapéutico , Resistencia a Antineoplásicos , Epirrubicina/uso terapéutico , Etopósido/uso terapéutico , Femenino , Humanos , Neoplasias Ováricas/metabolismoRESUMEN
Thirty cases of previously untreated advanced larynx carcinoma were checked for in vitro chemosensitivity and presence of the resistance markers viz. P-glycoprotein (P-gp) glutathione-S-transferase-pi (GST-pi) and protein kinase C (PKC) overexpression. The cytotoxicity testing was done using MTT assay and the resistance markers were checked by immunohistochemical methods using monoclonal antibodies. The drug combinations employed in MIT assay were 5FU* + MTX*, 5FU + cisPt*, 5FU + Mito*, cisPt + Mito and MTX + Mito (*5FU = 5Fluorouracil, MTX-methotrexate, cisPt-cisplatin and Mito = mitomycin C). No statistically significant correlation was observed between resistance to the above drug combinations and presence of the resistance markers under consideration. A statistically significant correlation was observed between node positivity and expression of resistance markers which indicates that presence of one or more of these markers in these tumors may be considered as a negative prognosis marker. CisPt-Mito was found to be the most effective drug combination in vitro, in the cases studied.
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Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/análisis , Antineoplásicos/toxicidad , Resistencia a Múltiples Medicamentos , Glutatión Transferasa/análisis , Neoplasias Laríngeas/patología , Proteína Quinasa C/análisis , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Supervivencia Celular/efectos de los fármacos , Cisplatino/toxicidad , Fluorouracilo/toxicidad , Regulación Neoplásica de la Expresión Génica , Glutatión Transferasa/genética , Humanos , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/cirugía , Metástasis Linfática , Metotrexato/toxicidad , Mitomicina/toxicidad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Proteína Quinasa C/genética , Células Tumorales CultivadasRESUMEN
P388/R, the adriamycin (ADR) resistant subline of murine P388 lymphocytic leukemia was cross-resistant to the drug mitoxantrone (MTN). One hour hyperthermia at 42 degrees C (HT) was employed along with ADR (10 micrograms/ml) and MTN (10 micrograms/ml) for circumventing the drug resistance of P388/R cells in in vitro-in vivo bioassays. Inhibition in the incorporation of tritiated thymidine into cellular DNA was measured to check the in vitro cytotoxic effect. Hyperthermia, ADR and MTN alone could not bring about significant degree of inhibition of DNA biosynthesis whereas the combination of ADR and MTN along with HT resulted in a synergistic cytotoxic action (p less than 0.001 and 0.01, respectively). The cells were treated with the drugs in vitro and inoculated into BDF1 mice. It was observed that ADR, MTN or HT pretreatment of the cells resulted in an increase of the life-span of the mice by 4.0-25.0%, 10-20% and 44-50%, respectively, whereas the pretreatment of cells with the combination of ADR and MTN with HT resulted in an increase by 104-125% and 212-220% in life-span of the mice, respectively. Studies revealed that the combination ADR-HT and MTN-HT resulted in circumvention of resistance of P388/R cells to ADR and MTN.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Hipertermia Inducida , Leucemia P388/terapia , Animales , Terapia Combinada , Doxorrubicina/administración & dosificación , Resistencia a Medicamentos/genética , Leucemia P388/genética , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Mitoxantrona/administración & dosificación , Timidina/metabolismo , Células Tumorales Cultivadas/efectos de los fármacosRESUMEN
Pentoxifylline (PTX) is a methylxanthine used clinically in the treatment of intermittent claudication. It is an active hemorheological agent used for the treatment of defective microcirculation. The use of the anticancer agent vincristine is limited by its toxicity to normal body tissues. The data presented in the present paper show that it is possible to achieve greater cell-kill by using vincristine in combination with pentoxifylline. The effect of pentoxifylline alone and in combination with vincristine was studied using membrane filtration technique in P388 leukemia (P388) and its subline P388/DOX resistant to doxorubicin and cross-resistant to vincristine. Pentoxifylline (100 mumol/l) had minimal inhibitory effect on DNA biosynthesis in P388 leukemia cells. Vincristine, at the concentration employed in this study did not show significant inhibition of DNA biosynthesis confirming multidrug resistant nature of P388/DOX cells. Pentoxifylline had a dose-sparing effect, wherein it enhanced the antiproliferative activity of vincristine at a clinically achievable concentration. The studies on reversibility of inhibition of DNA biosynthesis in P388/DOX cells pretreated with vincristine and pentoxifylline showed the irreversible nature of the effect of combination of vincristine and pentoxifylline. This observation warrants the possible use of pentoxifylline as an adjuvant in cancer chemotherapy.
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Replicación del ADN/efectos de los fármacos , Doxorrubicina/farmacología , Pentoxifilina/farmacología , Vincristina/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Resistencia a Medicamentos , Leucemia P388/patología , Ratones , Ratones Endogámicos DBA , Timidina/metabolismoRESUMEN
Adriamycin and mitoxantrone are known antitumor agents. The use of these agents is limited by their toxicity to normal body tissue. This paper shows that it is possible to achieve greater log cell-kill by using these drugs in combination with hyperthermia and diazepam. Experiments were carried out on 22 human chronic myeloid leukemia samples. 10 micrograms/ml adriamycin and 1 microgram/ml mitoxantrone were used in combination with hyperthermia 42 degrees C, for 3 h and 1 h respectively, with and without diazepam (1 microgram/ml). Inhibition of incorporation of radiolabeled nucleic acid precursor (3H-thymidine) in treated cells as compared to the untreated cells was used as a measure of cytotoxicity. The statistical evaluation of the data shows that the enhancement of drug cytotoxicity due to hyperthermia and diazepam is highly significant (p less than 0.001) in case of both the drugs.
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Diazepam/farmacología , Doxorrubicina/toxicidad , Calor , Leucemia Mieloide/tratamiento farmacológico , Mitoxantrona/toxicidad , Supervivencia Celular/efectos de los fármacos , Humanos , Técnicas In VitroRESUMEN
Mitoxantrone, a new anticancer drug has DNA-binding properties similar to anthracycline antibiotics. In the present studies, effect of the drug has been tested in vitro on human chronic myeloid leukemia cells at 37 degrees C and 42 degrees C. Inhibition of 3H-tritiated thymidine incorporation in the drug-treated cells compared with untreated cells has been used as the parameter of cytotoxicity of the drug and hyperthermia. Cell samples from 11 CML patients who did not receive any chemotherapy showed less response to the drug at 0.5 micrograms/ml and 1 microgram/ml at 37 degrees C. Exposure of CML cells to 42 degrees C for 2 h indicated 13 to 44% inhibition in 3H-TdR incorporation. However, when CML cells were exposed to mitoxantrone for 2 h at 42 degrees C the 3H-thymidine incorporation was inhibited to the extent of 27 to 71%, indicating greater cellular damage with this combination.
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Antineoplásicos/toxicidad , Replicación del ADN , Calor , Leucemia Mieloide/sangre , Mitoxantrona/toxicidad , Supervivencia Celular/efectos de los fármacos , Terapia Combinada , Replicación del ADN/efectos de los fármacos , Humanos , Técnicas In Vitro , Leucemia Mieloide/terapia , Timidina/metabolismoRESUMEN
Phyllanthus niruri has been found to exhibit marked inhibitory effect on hepatitis B virus evident by its exhaustive utility in cases of chronic jaundice. However, till date, research has not been focused on identification and validation of active pharmacophores of Phyllanthus niruri responsible for the reported inhibitory effect of its aqueous extract on anti-human immunodeficiency virus. The present investigation examines the anti-HIV effects of the alkaloidal extract of Phyllanthus niruri in human cell lines. The inhibitory effect on HIV replication was monitored in terms of inhibition of virus induced cytopathogenecity in MT-4 cells. The alkaloidal extract of Phyllanthus niruri showed suppressing activity on strains of HIV-1 cells cultured on MT-4 cell lines. The CC50 for the extract was found to be 279.85 microgmL(-1) whereas the EC50 was found to be 20.98 microgmL(-1). Interestingly the Selectivity Index (SI) was found to be 13.34, which showed a clear selective toxicity of the extract for the viral cells. The alkaloidal extract of Phyllanthus niruri was thus found to exhibit sensitive inhibitory response on cytopathic effects induced by both the strains of human immunodeficiency virus on human MT-4 cells in the tested concentrations.
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VIH/fisiología , Phyllanthus , Extractos Vegetales/farmacología , Replicación Viral/efectos de los fármacos , Células Cultivadas , HumanosRESUMEN
Aqueous extract of leaves of Nelumbo nucifera was investigated on acute stress (immobilization stress)-induced biochemical alterations in Swiss mice. The animals were also subjected to acute physical stress (swimming endurance test) and acute chemical stress (writhing test) to gauge the antistress potential of the extract. Further to evaluate the antistress activity of Nelumbo nucifera in chronic stress condition, fresh Wistar rats were subjected to cold restraint stress (4 degrees for 1 h) for 7 days after 21 days of pretreatment with the extract. Stimulation of hypothalamus pituitary adrenal axis in stressful condition alters plasma glucose, triglyceride, cholesterol, total protein and corticosterone levels. Pretreatment with the extract significantly ameliorated the stress-induced variations in these biochemical levels in both acute and chronic stress models. The extract treated animals showed increase in swimming endurance time and reduced number of writhes in physical and chemical-induced stress models respectively. Treatment groups also reverted back perturbed neurotransmitter levels (norepinephrine, dopamine and 5-hydroxytryptamine) in brain as well as increase in adrenal gland weights and atrophy of spleen caused by cold chronic stress. In mice immunized with sheep red blood cells, treatment groups subjected to restraint stress prevented the humoral immune response to the antigen. Histopathological studies of adrenal gland of stress control group revealed vacuolar degeneration, loss of architecture and formation of lesions in the cortex, which was reversed by extract treatment. The results indicate that aqueous extract of Nelumbo nucifera has significant adaptogenic activity against a variety of biochemical, histological, physiological and immunological perturbations in acute and chronic stress models.
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Chloramphenicol is an antimicrobial agent having a very broad-spectrum of activity including Gram-positive bacteria, Gram-negative bacteria and anaerobes. However the use of chloramphenicol has reduced over a period of time due to the adverse effects of causing bone marrow depression or in some cases severe aplastic anaemia. As the effects are seen on the bone marrow cell, it was intended to find out if these adverse effects could be used for the benefits in leukaemia patients, using in-vitro study on leukaemic cell lines. The study showed inhibition of growth of the leukaemia cells by chloramphenicol which was comparable to or better than daunorubicin in some cell lines. The article also discusses the other adverse effect profile of chloramphenicol compared with anticancer drugs and its potential benefit in leukaemia and in neutropenic fever.
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Antiinfecciosos/uso terapéutico , Antineoplásicos/uso terapéutico , Cloranfenicol/uso terapéutico , Leucemia/tratamiento farmacológico , Inhibidores de la Síntesis de la Proteína/uso terapéutico , Antiinfecciosos/efectos adversos , Antineoplásicos/efectos adversos , Cloranfenicol/efectos adversos , Humanos , Técnicas In Vitro , Inhibidores de la Síntesis de la Proteína/efectos adversosRESUMEN
The effect of adriamycin (ADR), vincristine (VCR), mitoxantrone (MTN) and cis-platin (PtCl) at acidic pH on the incorporation of 3H-thymidine (3H-TdR) was studied in vitro on P388 murine leukemia cells. The incorporation was inhibited at low pH by the four drugs used. In order to induce acidosis in tumor bearing mice, 6 g/kg glucose was administered intraperitoneally. The lowest pH that could be obtained was 6.8 two hours after glucose administration. The drugs ADR, VCR, MTN and PtCl administered to tumor-bearing mice 2 h following induction of acidosis resulted in significant increase in the life span of the tumor bearing mice.
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Acidosis/metabolismo , Antineoplásicos/farmacología , Supervivencia Celular/efectos de los fármacos , Acidosis/patología , Animales , Líquido Ascítico/metabolismo , ADN de Neoplasias/biosíntesis , Femenino , Glucosa/metabolismo , Concentración de Iones de Hidrógeno , Leucemia P388/metabolismo , Leucemia P388/patología , Masculino , Ratones , Ratones Endogámicos DBA , Ratones Endogámicos , Células Tumorales CultivadasRESUMEN
Selenium is known to inhibit growth rate of neoplastic cells. We have investigated the role of selenium (Se) in resensitization of the adriamycin (ADR) resistant murine P388/ADR cells to the action of ADR. The experiments were performed in the ADR sensitive parental P388 murine leukemia (P388/S) and its subline P388/ADR, resistant to ADR, developed in our laboratory. The effect of Se was observed to be dose dependent i.e. Se at a concentration of 5 x 10(-8)M resulted in potentiation of DNA biosynthesis whereas 5 x 10(-6)M and 5 x 10(-5)M Se resulted in inhibition of DNA-biosynthesis in P388/S cells. Along with ADR there was a further increase in inhibition of DNA biosynthesis. In P388/ADR cells, Se at 5 x 10(-6)M and 5 x 10(-8)M concentration resulted in inhibition of DNA biosynthesis, which increased further when combined with ADR indicating resensitization of these cells to the action of ADR. The inhibition was observed to be partially irreversible. These results were further confirmed in the in vivo and in vitro bioassays where the Se and Se+ ADR treatments resulted in increased lifespan of tumor bearing mice.
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Antibióticos Antineoplásicos/farmacología , Doxorrubicina/farmacología , Leucemia P388/patología , Selenio/toxicidad , Animales , División Celular/efectos de los fármacos , ADN/biosíntesis , Resistencia a Antineoplásicos , Ratones , Ratones Endogámicos DBA , Células Tumorales CultivadasRESUMEN
Doxorubicin (DOX) is a potent anticancer agent, the use of which is limited by its cumulative dose-dependent cardiotoxicity. Pentoxifylline (PTX) is a non-toxic methylxanthine used clinically for the treatment of intermittent claudication. It is an active haemorheological agent, used for the treatment of defective microcirculation. In the present study, we employed PTX as a drug response modulator in combination with DOX to achieve increased cytotoxicity in human chronic myeloid leukemia (CML) cells. Inhibition of 3H-TdR incorporation was used as a measure of cytotoxicity. PTX at 100 microM concentration significantly (P less than 0.001) potentiated DOX-mediated DNA biosynthesis inhibition in CML cells in vitro. Significant synergistic inhibition was seen in 13 out of 22 CML samples. Decreased DOX accumulation is a characteristic feature of DOX resistant tumor cell lines. Drug accumulation studies demonstrated that PTX significantly (P less than 0.02) increased the intracellular accumulation of DOX in the CML cells. The enhanced DOX accumulation can be a mechanism of increased cytotoxicity by DOX-PTX combination.
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Doxorrubicina/farmacología , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Pentoxifilina/farmacología , Doxorrubicina/administración & dosificación , Resistencia a Medicamentos , Sinergismo Farmacológico , Quimioterapia Combinada , Humanos , Pentoxifilina/administración & dosificación , Células Tumorales CultivadasRESUMEN
Thirty four patients with acute myeloid leukemia (AML) (30 de novo and 4 relapsed) were evaluated for P-glycoprotein (P-gp) expression, and in vitro chemosensitivity. The P-gp expression was evaluated by immunohistochemical method using JSB-1 monoclonal antibody and the results were visualized by peroxidase-antiperoxidase goat antimouse antibody and the in vitro chemosensitivity was measured by the semiautomated MTT colourimetric assay method. Depending upon the percent cells expressing P-gp and the intensity of P-gp staining, the samples were graded as absent, mild or strong for the relative P-gp expression, which was further correlated with the in vitro chemosensitivity and the clinical response of the tumors. Expression of P-gp was seen in 17 of the 30 de novo AML cases and all four relapse cases. Patients with no P-gp expression showed in vitro chemosensitivity while those with strong P-gp expression were resistant in vitro. Patients with mild P-gp expression showed varied chemosensitivity. P-gp expression correlated with clinical response to chemotherapy. Seven out of 11 patients with no P-gp achieved complete remission (C.R.). The other four died early in induction. Of five patients who expressed strong P-gp, four had resistant disease and the autopsy study of the remaining patient who died in induction revealed persistent disease. Of the 10 de novo AML patients who had mild P-gp expression, five achieved C.R. while one had resistant disease and four died in induction. All the four relapsed AML showed mild P-gp expression.(ABSTRACT TRUNCATED AT 250 WORDS)