Antitumor Effects of Ethanol Extract from Ventilago leiocarpa Benth on Sarcoma 180 Tumor-Bearing Mice and Possible Immune Mechanism / 中国结合医学杂志

OBJECTIVE@#To explore the antitumor effects of ethanol extract from Ventilago leiocarpa Benth (EEVLB) on sarcoma 180 (S180) tumor-bearing mice and the potential mechanism.@*METHODS@#Sixty mice were randomly assigned to 6 groups according to a random number table: normal group, model group, 5-fluorouracil (5-FU) group (0.02 g·kg@*RESULTS@#EEVLB with different concentrations achieved inhibition of tumor growth in vivo, wherein the high-dose group showed the most significant reduction in tumor weight and increased apoptosis of tumor cells (P<0.05). In addition, both net weight gain and spleen index of mice showed uptrend in EEVLB treatment groups (P<0.05). Besides, serum levels of IL-2 and IL-6, percentages of CD3@*CONCLUSIONS@#EEVLB exhibits promising antitumor activity in vivo. This effect might be due to activation of apoptotic signaling pathway, increase of cytokine levels and enhancement of immune function in tumor-bearing mice.

A polysaccharide fraction extracted from Pleurotus ostreatus mycelial biomass inhibit Sarcoma 180 tumor

ABSTRACT Fungi of Pleurotus genus have attracted a great interest due to their medicinal properties such as anti-inflammatory, antimicrobial and antitumor. These properties are attributed mainly to polysaccharides synthesized by Pleurotus. This work aimed to study the mycelial growth of P. ostreatus in submerged culture, evaluating the influence of the initial concentration of substrate (20 and 40 g/L of glucose) and the pH (4 and 6) on kinetic parameters of production of biomass. The effectiveness of different doses (10, 30 and 50 mg/kg) of a mycelium polysaccharide fraction extracted from P. ostreatus in reducing Sarcoma 180 development in mice was also verified. In the range of this study, maximum concentration of mycelial biomass (about 12.8 g/L) was obtained using 40.0 g/L of glucose, at pH 4.0. The total biomass productivity (Px) was not significantly affected by substrate concentration and pH, reaching values of 0.034 g/L.h. Sarcoma 180 tumor weight was reduced in 74.1, 75.5 and 53.7% when 10, 30 and 50 mg/kg were administered, respectively. These results show the high antitumor potential of intracellular polysaccharide fraction of mycelial biomass of P. ostreatus, particularly at lower doses of 10 and 30 mg/kg.

Indigofera suffruticosa Mill (Fabaceae): hepatic responses in mice bearing sarcoma 180 / Indigofera suffruticosa Mill (Fabaceae): respuestas hepáticas en ratones portadores de sarcoma 180

Indigofera suffruticosa is a plant generally used to treat infectious and inflammatory processes. This work aims to evaluate the histopathological changes in the liver tissue of mice with Sarcoma 180 after subchronic treatment with aqueous extract obtained by infusion and maceration of Indigofera suffruticosa leaves. Male mice were divided into four groups of six animals: G1, G2 and G3 patients with Sarcoma 180 and Sarcoma 180 G4 without sarcoma. G1 and G2 were treated with infusion mashing respectively (50 mg/kg ip); G3 and G4 controls received saline (15 ml/kg ip). The histopathological and morphometric analysis of liver tissue after subchronic treatment with aqueous extracts by infusion and maceration of the groups G1, G2 and G4 were similar and showed no degraded areas or leukocyte infiltration compared to G3, which shows a marked destruction of liver architecture. The results showed that after subchronic treatment with the aqueous extract of leaves Indigofera Suffruticosa obtained by infusion and maceration, the hepatic architecture was preserved, suggesting its use as an alternative hepatoprotective agent.

Indigofera suffruticosa es una planta utilizada para tratar procesos infecciosos e inflamatorios. Este trabajo tiene como objetivo evaluar los cambios histopatológicos en el tejido del hígado de ratones con sarcoma 180 después del tratamiento subcrónica con el extracto acuoso obtenido por infusión y maceración de las hojas de Indigofera suffruticosa. Los ratones machos fueron divididos en cuatro grupos de seis animales: pacientes G1 , G2 y G3 con Sarcoma 180 y G4 sin Sarcoma. G1 y G2 fueron tratados con infusión de maceración respectivamente (50mg/kg.ip); Controles G3 y G4 recibieron solución salina (15 ml/kg.ip). El análisis histopatológico y morfométrico de tejido hepático después de un tratamiento subcrónico con extractos acuosos por infusión y la maceración de los grupos G1, G2 y G4 fueron similares y no mostraron áreas degradadas o la infiltración de leucocitos en comparación a G3, que muestra una marcada destrucción de la arquitectura del hígado. Los resultados mostraron que después de un tratamiento subcrónico con el extracto acuoso de hojas de Indigofera suffruticosa obtenidos por infusión y la maceración, se conservó la arquitectura hepática, lo que sugiere su uso como una alternativa de agente hepatoprotector.

Response of S 180 murine tumor to bleomycin in combination with radiation and hyperthermia using micronucleus assay: a multimodality approach for therapeutic augmentation.

Response of a transplantable tumor, S180, grown intradermally in inbred Balb/c mice, was assessed by using micronucleus assay after treating the solid tumors with bleomycin (BLM), radiation (RT) and hyperthermia (HT) vis-a-vis multimodality approach. The frequency of micronuclei (MN) though did not vary greatly during the one week of observation in untreated tumors, it significantly increased in the drug and RT groups at 24 hr post-treatment. However, MN frequency was non-significant in the HT group from the control. A drug dose dependent linear increase in the frequency of MN induction was evident in 10, 15 and 20 mg/kg body weight BLM alone treated groups. Combination of radiation with BLM or HT further increased the MN counts in the bimodality groups. But, MN induction at 24 hr post-treatment in the trimodality group (BLM + RT + HT) was non-significant from that of the bimodality treatments. However, the tumors treated with trimodality treatment presented severe tumor necrosis, indicating increased cell loss, and resulting in immediate tumor regression. In all the bi-modality groups MN counts though declined 3 or 5 days post-treatment, the values remained significantly higher than the control, on day 7 post-treatment. Micronucleus assay could be used as a predictive parameter for the assessment of post-irradiation tumor regression response. However, the tumor response assessment with MN assay alone may not be sufficient and the role of other parameters, such as apoptosis and necrosis, in immediate tumor regression, especially radiosensitive/thermosensitive tumors can not be ignored while taking multimodality approach into consideration for cancer therapy.

Efficacies of plant phenolic compounds on sodium butyrate induced anti-tumour activity.

The ability of the differentiation inducing agent sodium butyrate (NaB) alone or combined with plant-derived phenolic compounds to produce growth inhibition in human erythroleukemic cells was investigated. As a single agent, curcumin produced a marked inhibition of proliferation indicated by its low concentration used. The effect of phenolics on the cell cycle could probably contribute to the augmented antiproliferative activity of NaB. The present data show that quercetin produced synergistic effect in terms of cell killing in association with NaB. Both curcumin and ferulic acid potentiated NaB-induced reduction of cell number. When NaB was added before exposure to graded doses of quercetin it did induce a greater inhibitory effect. The combination of NaB and quercetin seems less effective on S180 ascites tumour cells. As a single agent quercetin was found to be the most efficacious on S180 tumour model.

Antitumor activity of Hygrophila spinosa on Ehrlich ascites carcinoma and sarcoma-180 induced mice.

Petroleum ether extract from H. spinosa root exhibited antitumor activity in Ehrlich ascites carcinoma and Sarcoma-180 bearing mice Processed extract suppressed significantly the tumor fluid volume at the end of 3 weeks experiment. It decreased about 50% of packed cell volume and increased life span of EAC/S-180 bearing mice in a day dependent manner. Red blood cell count, hemoglobin content and white blood cell count were more or less normal after processed extract treatment of the tumor bearing mice. In tumor control animals, neutrophils increased (273.7% in EAC and 263.4% in S-180 bearing mice respectively with respect to normal mice) whereas lymphocytes decreased (60.0% in EAC and 56.5% in S-180 bearing mice respectively with respect to normal mice). It also inhibited the rapid increase of body weight of tumor bearing mice.

Withania somnifera Dunal (Ashwagandha): potential plant source of a promising drug for cancer chemotherapy and radiosensitization.

Study of antitumor and radiosensitizing properties of W. somnifera (Ashwagandha), a well known medicinal plant, have yielded encouraging results. The alcoholic extract of the dried roots of the plant as well as the active component withaferin A isolated from the extract showed significant antitumor and radiosensitizing effects in experimental tumors in vivo, without any noticeable systemic toxicity. Withaferin A gave a sensitizer enhancement ratio of 1.5 for in vitro cell killing of V79 Chinese hamster cells at a non toxic concentration of approximately 2 microM. The mechanism of action of this compound is not known. The studies so far indicate that W. somnifera could prove to be a good natural source of a potent and relatively safe radiosensitizer/chemotherapeutic agent. Further studies are needed to explore the clinical potential of this plant for cancer therapy.

Toxicity and antitumor activity of niosomal bleomycin in tumor bearing mice.

Niosomal encapsulation of bleomycin enhanced the antitumor activity against Ehrilich ascites and sarcoma-180 models. The niosomal/free drug mean survival time values of 1.28 was achieved in Ehrlich ascites infected animals. Niosomal bleomycin considerably increased the 40 days survival rate in mice. Tumor volume doubling time of S-180 tumor was also increased significantly in niosomal treated animals. Histopathological studies of lung and jejunum of Niosomal bleomycin treated mice, confirmed the less toxic potential of encapsulated bleomycin. The suppression of peripheral and bone marrow WBC counts upon niosomal bleomycin treatment was not substantial.

In vivo tumor inhibitory and radiosensitizing effects of an Indian medicinal plant, Plumbago rosea on experimental mouse tumors.

Tumor growth inhibitory and radiosensitizing effects of the alcoholic root extract of P. rosea was studied on experimental mouse tumors, S-180 solid tumor and Ehrlich ascites carcinoma in vivo. Intraperitoneal injection of 50 mg/kg of Plumbago extract (PE) for 10 days starting from 24 hr after intradermal inoculation of S-180 cells in BALB/c mice produced about 16% complete response (CR). The CR% increased with increase in drug dose, to 50% at 100 mg/kg for 10 days. As 100 mg/kg produced toxic side effects, lower doses were used with other treatment modalities, radiation (RT) and hyperthermia (HT). Treatment of 50 mm3 tumor with PE (75 mg/kg) for 10 days with local RT (10 Gy) and/or HT (43 degrees C, 30 min) subadditively increased the CR% and tumor free survival. The combination also significantly reduced the growth rates of uncured tumors. The PE significantly reduced the tumor glutathione content and this effect was markedly enhanced by the combination of the three modalities. PE alone was not very effective in preventing the growth of Ehrlich ascites carcinoma in Swiss mice, though it increased mean survival time and ILS% of the mice. But with radiation it produced a synergistic effect in increasing the tumor inhibition and 120 day animal survival from 10% to 50%. The results demonstrate that though PE may have only a weak antitumor effect, it may be a good candidate for use with radiation to enhance the tumor killing effect.

Antitumor and radiosensitizing effects of Withania somnifera (Ashwagandha) on a transplantable mouse tumor, Sarcoma-180.

Antitumor and radiosensitizing effects of alcoholic root extract of W. somnifera and their modification by heat were studied in vivo on Sarcoma-180 grown on the dorsum of adult BALB/c mouse. Ashwagandha (AT) was injected (ip) at a dose of 500 mg/kg body wt for 10 consecutive days into mouse bearing tumor of 50 +/- 5 mm3, with or without a local treatment of 10 Gy gamma radiation (RT) or hyperthermia at 43 degrees C for 30 min (HT) or both on 5th day of AT. The response was assessed on the basis of tumor regression, growth delay, animal survival and changes in the tumor GSH content. Ashwagandha, RT and HT individually produced 18, 38 and 45% complete response (CR) respectively, but RT gave the best long term survival. Ashwagandha increased the effect of radiation on tumor regression as well as growth delay, but AT + HT gave a better tumor cure. However, both these combinations gave almost identical long term survival, which was not much higher than that produced by RT alone. The combination of Ashwagandha for 10 days with one local exposure to RT followed by HT significantly increased the tumor cure, growth delay of partially responding tumors and animal survival. This combination also significantly and synergistically depleted the tumor GSH level, with no recovery even at 3 hr after treatment. It is concluded that Ashwagandha, in addition to having a tumor inhibitory effect, also acts as a radiosensitizer and heat enhances these effects. The severe depletion in the tumor GSH content by the combination treatment must have enhanced the tumor response, as the inherent protection by the thiol will be highly reduced.

In vivo growth inhibitory effect of Withania somnifera (Ashwagandha) on a transplantable mouse tumor, Sarcoma 180.

Withania somnifera is a medicinal plant used in the treatment of a variety of ailments in the Ayurvedic system. Alcoholic extract of the root of the plant was injected(ip) at daily doses of 200 to 1000 mg/kg body wt for 15 days starting from 24 hr after intradermal inoculation of 5 x 10(5) cells of S-180 in BALB/c mice. Solid tumor growth was monitored for 100 days. Doses of 400 mg/kg and above produced complete regression of tumor after an initial growth, the percentage of complete response (CR) increasing with increasing drug dose. A 55% CR was obtained at 1000 mg/kg drug administration, but this dose also produced some mortality among the animals. A significant increase in the volume doubling time and growth delay was seen when the drug dose was increased from 500 to 750 mg/kg body wt, but further increase in drug dose to 1000 mg/kg did not produce any significant increase in these responses. Cumulative doses of 7.5 to 10 g at daily doses of 500 or 750 mg/kg seems to produce a good response in this tumor.

Efficacy of 5-fluorouracil in combination with methoxyphenyl maleamic acid in murine tumors.

Combination chemotherapy studies were carried out in vivo against sarcoma 180 (ascites)(S180) and Ehrlich (ascites) carcinoma (EAC) tumours using cytotoxic drugs and methoxyphenyl maleamic acid (MPMA), an intermediate in the synthesis of pyrrolidine-nitrogen-mustards. Preliminary data have suggested that the combination of 5-fluorouracil (5-FU) and methoxyphenyl maleamic acid (MPMA) was more active than 5-FU used singly against EAC tumour. The possible therapeutic potential of this combination was further investigated in EAC tumour.

Combined effect of cyclophosphamide and extracts of Crotalaria and Senecio plants on experimental tumours.

The combined effect of cyclophosphamide (CTX) and extracts of six patients belonging to Crotalaria and Senecio genera was assessed on experimental transplantable S180 (both ascitic and solid forms) tumour. Successive petroleum ether and methanolic extracts from these plants were obtained. The combined administration of CTX and petroleum ether extract of C. albida and the methanolic extracts of C. albida, S. chrysanthemoides, S. densiflorus and S. jacquemontianus led to prolonging the life span of S180 (ascitic) tumour bearing mice. The data indicate that the most effective extract in combination with CTX was the methanolic extract of S. chrysanthemoides. The extracts alone had no effect on survival of tumour-bearing mice. The same extracts and the same combinations had no effect on S180 solid tumour.

Antitumoral activity of polysaccharide isolated from Cyttaria johowii on the growth of sarcoma 180 in normal and splenectomized mice

Se estudió la actividad antitumoral del polisacárido PCj3 aislado del hongo Cyttaria johowii sobre el crecimiento de Sarcoma 180 (S180) sólido en ratones BALB/c normales y esolenectomizados, observando que este tratamiento inhibió el desarrollo del tumor tanto en ratones normales como esplenectomizados. Simultáneamente se evaluó el efecto del PCj3 sobre las poblaciones leucocitarias de sangre periférica al 8§, 15§ y 25§ día del experimento. Los resultados obtenidos al 8§ día muestran que todos los grupos inoculados con S180 sufrieron un incremento del número de linfocitos y neutrófilos, correspondiendo la cifra superior a los animales esplenectomizados desafiados con S180 y tratados con PCj3. El incremento de neutrófilos continuó en todos los animales con o sin tratamiento con PCj3 hasta el final del experimento, mientras que la linfocitosis sólo se mantuvo en los grupos esplenectomizados. El tratamiento con PCj3 causó un incremento del número de monocitos respecto al valor normal al 8§ día. Concluimos de acuerdo con estas observaciones que la actividad antitumoral del PCj3 fue más significativa en los ratones esplenectomizados, incrementando además este tratamiento los días de sobrevida, así como los valores de linfocitos, neutrófilos y monocitos en el 8§ día del crecimiento tumoral con respecto a los otros grupos

Açäo antimicrobiana e antitumoral de glicosídeos isolados de Ipomoea bahiensis / Antimicrobial and anti-tumoral activity of isolated glycosides of Ipomoea bahiensis

Quatro glicosídeos isolados de Ipomoea bahiensis, derivados dos ácidos 11 hidroxihexadecanóico e 11-hidroxitetradecanóico, apresentam boa atividade contra representantes de microrganismos Gram-positivos. O composto (la) também inibe significativamente o crescimento do Sarcoma 180 a doses entre 7,5 e 10,0 mg/kg