Nerve Growth Factor from Cobra Venom Inhibits the Growth of Ehrlich Tumor in Mice

The effects of nerve growth factor (NGF) from cobra venom (cvNGF) on growth of Ehrlich ascites carcinoma (EAC) cells inoculated subcutaneously in mice have been studied. The carcinoma growth slows down, but does not stop, during a course of cvNGF injections and restores after the course has been discontinued. The maximal anti-tumor effect has been observed at a dose of 8 nmoles cvNGF/kg body weight. cvNGF does not impact on lifespan of mice with grafted EAC cells. K252a, a tyrosine kinase inhibitor, attenuates the anti-tumor effect of cvNGF indicating the involvement of TrkA receptors in the process. cvNGF has induced also increase in body weight of the experimental animals. In overall, cvNGF shows the anti-tumor and weight-increasing effects which are opposite to those described for mammalian NGF (mNGF). However in experiments on breast cancer cell line MCF-7 cvNGF showed the same proliferative effects as mNGF and had no cytotoxic action on tumor cells in vitro. These data suggest that cvNGF slows down EAC growth via an indirect mechanism in which TrkA receptors are involved.     

Ameliorative effects of vitamin B17 on the kidney against Ehrlich ascites carcinoma induced renal toxicity in mice

Cancer is the major cause of death and many factors that lead to its occurrences, such as environmental pollution and pesticides and other factors. Ehrlich carcinoma development depends on many things associated with the environment, nutrition, personal habits, and family history. The present study aimed to evaluate the potential protective effects of vitamin B17 (VB17) against Ehrlich ascites carcinoma (EAC) that induced kidney toxicity in female mice. The mice were divided into five groups (first group, control group; second group, VB17 group; third group, EAC group; fourth group, pretreated EAC with VB17; fifth group, cotreated EAC with VB17). Results showed the VB17 in pretreated (G4) and cotreated (G5) groups lead to an improvement in DNA damage and cytological examination, in addition significantly (P < .05) increase in Na⁺, red blood cell, hemoglobin, hematocrit value, mean corpuscular hemoglobin (MCH), and MCH concentration, whereas significantly (P < .05) decrease in urea, creatinine, K⁺, platelets, and white blood cells while insignificant (P < .05) changes in mean corpuscular volume when compared to the EAC group. Many histopathological changes were observed in kidney sections in EAC as marked damage and degenerated, glomerular atrophy, the Malpighian corpuscles that lost their characteristic configuration. On the other hand, a moderate improvement and arrangement in the kidney histological structure in pretreated VB17 + EAC, while a mild enhancement and arrangement of the kidney structure in cotreated EAC + VB17. In addition, depletion in renal P53 and PCNA protein expression compared with the EAC group. It could be concluded that VB17 has a potential renal protective effect against EAC cells induced kidney injury.     

Effect of berberine on proliferation, biosynthesis of macromolecules, cell cycle and induction of intercalation with DNA, dsDNA damage and apoptosis in Ehrlich ascites carcinoma cells

Our primary aim was to study berberine, a potential anti-cancer drug, for its cytotoxic and antiproliferative activity in-vitro using Ehrlich ascites carcinoma (EAC) cells. Cytotoxicity was measured by the growth inhibition assay. We investigated the effect of berberine on the biosynthesis of macro-molecules (DNA, RNA, proteins), cell cycle effects and induction of dsDNA damage and apoptosis in berberine-treated EAC cells. Our results showed that berberine acts cytotoxically on EAC cells. The cytotoxicity was directly concentration and time dependent. The highest cytotoxic concentrations (100 and 50 microg mL(-1)) induced intercalation of berberine with DNA, formation of dsDNA breaks, inhibition of DNA synthesis and death of EAC cells. A concentration of 10 mug mL(-1) induced clear apoptotic cell death, which was followed by inhibition of protein synthesis.     

阿霉素对艾氏腹水癌细胞产生多药抗药性的研究

用对阿霉素较为敏感的艾氏腹水癌在小鼠体内用阿霉素进行长达50 wk的治疗,致使EAC细胞对阿霉素产生抗药性.抗药性细胞的生长比敏感株缓慢,每只小鼠体内总的瘤细胞体积,细胞计数,及平均单一细胞体积均比敏感株明显为小,同时还发现染色体匀染及双微体结构.该模型对长春新碱,放线菌素D.及丝裂霉素C均产生交叉抗药性,对VP-16产生部分交叉抗药性.而对冬凌草甲素则无交叉抗药性.     

Antitumor and antioxidant activity of Polyalthia longifolia stem bark ethanol extract

In the present study, the ethanol extract of stem bark of Polyalthia longifolia Benth. and Hook (Annonaceae) was screened for its in vitro and in vivo antitumor activity. In vitro cytotoxicity of P. longifolia extract was assessed in murine cancer cells and in human cancer cells by Trypan blue exclusion assay and MTT assay, respectively. P. longifolia extract showed concentration-dependent cytotoxicity in Ehrlich’s ascites carcinoma (EAC) and Dalton’s ascites lymphoma (DLA) cells with IC₅₀ values of 45.77 and 52.52?µg/mL, respectively. In the MTT assay, the IC₅₀ values of P. longifolia extract against HeLa and MCF-7 cells were 25.24 and 50.49 µg/mL, respectively. In vivo antitumor activity against Ehrlich’s ascites tumor and Dalton’s solid tumor models was assessed by administering 50 and 100?mg/kg of P. longifolia extract, i.p., for 7 consecutive days. P. longifolia extract, at a dose of 100?mg/kg, significantly enhanced mean survival time (MST) and marginally improved hematological parameters when compared to EAC control mice. And the same dose significantly reduced the tumor volume as compared to control DLA inoculated mice. Positive control, cisplatin (3.5?mg/kg, i.p., single dose), significantly enhanced MST and improved hematological parameters when compared to EAC and significantly reduced the tumor volume when compared to DLA control. In vitro antioxidant potential of P. longifolia extract was also determined owing to the role of reactive oxygen species in tumor initiation and progression. P. longifolia extract scavenged DPPH radicals, reduced ferric ions and inhibited lipid peroxidation with IC₅₀ values of 18.14, 155.41 and 73.33 µg/mL, respectively.     

Cobalt oxide nanoparticles induced oxidative stress linked to activation of TNF‐α/caspase‐8/p38‐MAPK signaling in human leukemia cells

The purpose of this study was to determine the intracellular signaling transduction pathways involved in oxidative stress induced by nanoparticles in cancer cells. Activation of reactive oxygen species (ROS) has some therapeutic benefits in arresting the growth of cancer cells. Cobalt oxide nanoparticles (CoO NPs) are an interesting compound for oxidative cancer therapy. Our results showed that CoO NPs elicited a significant (P <0.05) amount of ROS in cancer cells. Co‐treatment with N‐aceyltine cystine (an inhibitor of ROS) had a protective role in cancer cell death induced by CoO NPs. In cultured cells, the elevated level of tumor necrosis factor‐alpha (TNF‐α) was noted after CoO NPs treatment. This TNF‐α persuaded activation of caspase‐8 followed by phosphorylation of p38 mitogen‐activated protein kinase and induced cell death. This study showed that CoO NPs induced oxidative stress and activated the signaling pathway of TNF‐α‐Caspase‐8‐p38‐Caspase‐3 to cancer cells. Copyright © 2015 John Wiley & Sons, Ltd.     

Allicin enhances chemotherapeutic response and ameliorates tamoxifen-induced liver injury in experimental animals

Context: Tamoxifen (TAM) is widely used for treatment of hormone-dependent breast cancer; however, it may be accompanied with hepatic injury. Allicin is the most abundant thiosulfinate molecule from garlic with the potential to provide beneficial effects on various diseases.

Objective: To elucidate the effect of commercially available allicin on both antitumor activity and liver injury of TAM.

Materials and methods: The cytotoxicity of TAM and/or allicin was evaluated in vitro using cultured Ehrlich ascites carcinoma (EAC) cells and in vivo against murine tumor (solid) model of EAC. TAM induced liver injury in rats by intraperitoneally (i.p.) injection at a dose of 45?mg/kg, for 7 successive days.

Results: TAM at a dose of 3?µM (IC₅₀) significantly decreased percent survival of EAC to 52%. TAM combination with allicin (5 or 10?µM) showed a significant cytotoxic effect compared with the TAM-treated group as manifested by a decrease in percent survival of EAC to 35% and 29%, respectively. Allicin (10?mg/kg, orally) enhanced the efficacy of TAM (1?mg/kg, i.p.) in mice as manifested by a significant increase in solid tumor growth inhibition by 82% compared with 70% in the TAM group. In rats, TAM intoxication resulted in a significant decline in SOD, GSH, and total protein with significant elevation in TBARS, ALT and AST, ALP, LDH, total bilirubin, γGT, and TNF-α levels. These changes are abrogated by allicin treatment.

Discussion and conclusion: The results suggest the beneficial role of allicin as an adjuvant to TAM in cancer treatment by alleviating liver injury.     

Synthesis and evaluation of curcumin analogues as cytotoxic agents

Seventeen curcumin analogues were prepared and evaluated for in vitro and in vivo cytotoxicity against an Ehrlich ascites carcinoma (EAC). In vitro results revealed that compounds 10, 7, and 12 were the most potent analogues against EAC respectively. However, in vivo evaluation of compound 10 proved its capability to normalize the blood picture compared with 5-fluorouracil, a well-known anticancer drug.     

甲氨蝶呤吸干乳剂的抗肿瘤作用

用吸干乳剂作为抗癌药物甲氨蝶呤 (MTX)的载体 ,考察MTX对S1 80 、H2 2 、ESC 3种实体瘤和EAC腹水瘤的抑制作用 ,并初步考察了MTX制成吸干乳剂后对小鼠的毒性 .结果表明 :与MTX片剂相比 ,吸干乳剂能提高MTX对 3种实体瘤和EAC的抑制作用     

Antioxidant and hepatoprotective activity of the methanol extract of <Emphasis Type="Italic">Careya arborea</Emphasis> bark in Ehrlich ascites carcinoma-bearing mice

The methanol extract of Careya arborea bark (MECA) was tested for antioxidant and hepatoprotective activity in Ehrlich ascites carcinoma (EAC) tumor-bearing mice. Tumor control animals inoculated with EAC showed a significant alteration in the levels of antioxidant and hepatoprotective parameters. The extract treatment at 50, 100 and 200 mg/kg body weight doses given orally caused a significant reversal of these biochemical changes towards the normal in serum, liver and kidney when compared to tumor control animals indicating the potent antioxidant and hepatoprotective nature of the standardized extract.     

Antitumour Activity of Bauhinia variegata Against Ehrlich Ascites Carcinoma Induced Mice

The antitumour activity of ethanol extract of Bauhinia variegata (EBV) has been evaluated against Ehrlich ascites carcinoma (EAC) in Swiss albino mice. A significant enhancement of mean survival time of EBV treated tumour bearing mice was found with respect to the control group. EBV treatment was found to enhance peritoneal cell counts. After 14 days of inoculation, EBV is able to reverse the changes in the haemotological parameters, protein and PCV consequent to tumour inoculation. Oral administration of EBV was effective in reducing solid tumour mass development induced by EAC cells. EBV was found to be a potent cytotoxic towards EAC tumour cells.     

Synthesis and antitumor evaluation of selected 5,6-disubstituted 1(2)H-indazole-4,7-diones

A series of novel aziridinyl-substituted 1(2)H-indazole-4,7-diones and related 1(2)H-indazole-4,7-diones was synthesized and tested against Ehrlich ascites carcinoma growth in male CF1 mice. Ten of the test compounds, including two aziridinyl-substituted 1(2)H-indazole-4,7-diones, were found to be significantly active (inhibition of tumor growth greater than 80%) in the Ehrlich ascites carcinoma screen. Several structure-activity relationships were indicated for antitumor activity in this screen. An aziridinyl-substituted derivative, 5-aziridinyl-6-chloro-1H-indazole-4,7-dione (8a), also exhibited significant activity against the growth of P-388 lymphocytic leukemia cells in male BDF1 mice (% T/C = 145; % T/C greater than 125 is considered significant).     

Impact of zinc oxide nanoparticles on thioredoxin‐interacting protein and asymmetric dimethylarginine as biochemical indicators of cardiovascular disorders in gamma‐irradiated rats

Nanoparticle is a microscopic particle that has been existed in a wide range of biotechnological purposes. Zinc oxide nanoparticles (ZnO‐NPs) have fewer environmental hazards and have shown positive impacts in the medical field. This work aimed to observe the effects of low and high doses of ZnO‐NPs on heart injury induced by ionizing radiation (IR). Animals were irradiated by 8 Gy of gamma rays and ZnO‐NPs (10 and 300 mg/Kg/day) were orally delivered to rats 1 hour after irradiation. Animals were dissected on 15th day postirradiation. Data showed that the oxidative damage resulted from radiation exposure, appeared by marked increments in the malondialdehyde (MDA) content and the level and protein expression of thioredoxin‐interacting protein (TXNIP) with a noticeable decline in the level and expression of thioredoxin 1 (Trx‐1) and thioredoxin reductase (TrxR), as well as glutathione (GSH) level and the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Moreover, radiation‐induced inflammation, manifested by a noticeable elevation in the level of tumor necrotic factor‐alpha (TNF‐α), interleukin‐18 (IL‐18), and C‐reactive protein (CRP). Additionally, endothelial dysfunction marked with a high level of asymmetric dimethylarginine (ADMA), total nitrite/nitrate (NOx), intercellular adhesion molecule 1 (ICAM‐1), homocysteine (Hcy), creatine kinase (CK‐MB), cardiac troponin‐I (cTn‐I), and lactate dehydrogenase (LDH). In addition, a decrease of zinc (Zn) level in the cardiac tissue was recorded. ZnO‐NPs treatment (10 mg/kg) mitigated the oxidative stress and inflammation effects on the cardiovascular tissue through the positive modulations in the studied parameters. In contrast, ZnO‐NPs treatment (300 mg/kg) induced cardiovascular toxicity of normal rats and elevated the deleterious effects of radiation. In conclusion, ZnO‐NPs at a low dose could mitigate the adverse effects on cardiovascular tissue induced by radiation during its applications, while the high dose showed morbidity and mortality in normal and irradiated rats.     

p38 alpha mitogen-activated protein kinase inhibition improves cardiac function and reduces myocardial damage in isoproterenol-induced acute myocardial injury in rats

p38 mitogen-activated protein (MAP) kinase is activated during ischemic/hypoxic myocardial injury. However, the role of activated p38 MAP kinase on cardiac function after myocardial injury is not well understood. In the present study, we investigated the cardioprotective effects of p38 MAP kinase inhibition in a rat model of acute myocardial injury, induced by subcutaneous injection of isoproterenol (ISO, 20 mg/kg/d for 3 days). A synthetic p38 alpha MAP kinase inhibitor, SD-282 (40 mg/kg) or vehicle (0.25% Tween 80 in saline) was given intraperitoneally twice a day for 3 days, concomitant with ISO treatment. Cardiac function, systolic blood pressure, gene expression including collagen I and III, fibronectin and COX-2, and the myocardial injury were analyzed. Results showed that administration of SD-282 remarkably improved ISO-induced reduction of cardiac function with increases in ejection fraction (P < 0.001), cardiac output (P < 0.05), stroke volume (P < 0.001), and cardiac index (P < 0.01). SD-282 abolished ISO-induced reduction of systolic blood pressure (106.7 +/- 2.2 versus 123.1 +/- 5.3 mm Hg, P < 0.05). The ISO-induced expression of COX-2, collagen I and III, and fibronectin genes was reduced significantly (P < 0.05 in all cases) by administration of SD-282. The myocardial injury induced by ISO was significantly reduced by the treatment of SD-282 as judged by the reduction of myocardial necrosis. Data suggest that p38 alpha MAP kinase may be involved in the pathogenesis of cardiac dysfunction in ischemic myocardial injury. Inhibition of this enzyme may improve cardiac function and protect myocardium from ischemic/hypoxic injury that occurs during ischemic heart disease.     

Antitumor agents. 16. Steroidal alpha-methylene-gamma-lactones.

Several novel steroidal alpha-methylene-gamma-lactones and related derivatives have been synthesized as potential steroid alkylating antitumor agents. The synthesis of these compounds involved the convenient Reformatsky-type reaction between ethyl-alpha-(bromomethyl)acrylate and the proper steroidal ketones. In vitro assay for the cytotoxicity of these compounds against the growth of tissue culture cells originating from human epidermoid carcinoma of the larynx (H.Ep.-2) has shown significant activity. Cytotoxicity was improved at least sixfold with the introduction of lipophilic steroidal character. Preliminary in vivo tumor assay also indicated that these compounds were active against Walker 256 carcinosarcoma in rats and were inactive against both L1210 lymphoid leukemia and Ehrlich ascites carcinoma in mice. However, the simple alpha-methylene-beta,beta-dicarbethoxy-gamma-butyrolactone significantly inhibited Ehrlich ascites tumor growth.     

Anti-tumor effect of 3-amino-N-substituted-pyrrolidine-2,5-dione-N-mustard hydrochloride.

The anti-tumor effect of 3-amino-N-substituted pyrrolidine-2,5-dione-N-mustard hydrochloride (PNM.HCl) against Ehrlich (ascites) carcinoma (EAC) was studied. A substantial increase in the survival of mice bearing EAC tumor was achieved following daily administration of PNM.HCl at subtoxic dosages. The therapeutic efficacy of PNM.HCl was maintained with changes in dosages and the schedules of administration. The effect of PNM.HCl when administered with conventional anti-cancer drugs at different time schedules against EAC was also studied. The results demonstrated an augmentation of anti-tumor activity in the case of certain anti-cancer drugs against EAC tumor, thereby suggesting a potential usefulness of PNM.HCl in multi-drug therapy.     

Trichosanthes dioica root extract induces tumor proliferation and attenuation of antioxidant system in albino mice bearing Ehrlich ascites carcinoma

Trichosanthes dioica Roxb. (Cucurbitaceae), called pointed gourd in English, is a dioecious climber grown widely in the Indian subcontinent. The present study assessed the influence of treatment of hydroalcoholic extract of Trichosanthes dioica root (TDA) on Ehrlich ascites carcinoma (EAC) in Swiss albino mice with effects on antioxidant systems. Twenty-four hours after intraperitoneal inoculation of tumor (EAC) cells in mice, TDA was administered at 25 and 50 mg/kg for 8 consecutive days. On the 9(th) day, half of the mice were sacrificed for estimation of tumor proliferation, hematological, and hepatic antioxidative parameters. The rest were kept for assessment of survival parameters. TDA exhibited dose dependent and significant increase in tumor weight, tumor volume, packed cell volume and viable cells and reduced non-viable cells and life span of EAC bearing animals. Hematological parameters were significantly worsened in TDA-treated mice. TDA treatment significantly aggravated the hepatic antioxidative parameters. The present study demonstrated that T. dioica root possessed tumor promoting activity in EAC bearing albino mice, plausibly mediated by attenuation of endogenous antioxidant systems.     

抗肿瘤药物的研究 ⅩⅣ.锑胺羧螯合物化学结构与疗效间关系的探討

銻胺羧螯合物是本所发現的新型抗肿瘤药物,本文继續探討此类化合物的化学結构与疗效之間关系。发現:(1)銻与5种不同类型的胺羧螯合剂結合的制剂,例如EDTA-Sb(Ⅰ)和PDTA-Sb(Ⅳ)的不同盐类,N取代的EDTA-Sb(Ⅱ),ATA-Sb(Ⅴa)及其类似物(Ⅶ)和GDTA-Sb(Ⅸf)对小鼠Ehrlich腹水瘤均有明显的抑制作用,其中乙二胺四乙酸銻丙基銨盐和对氧氮六环盐的疗效較其鈉盐为佳。(2)汞、鉍、鉛、鋅、錳、銅、鈷、鎳、錫和鋇10种金属胺羧絡合物(Ⅲ,Ⅴ及Ⅷ)及EDTA,PDTA和ATA对Ehrlich腹水瘤和肉瘤180均无疗效。(3)EDTA-Sb-Na,PDTA-Sb-Na和ATA-Sb对肉瘤180稍有抑制作用。(4)銻胺羧螯合物抗癌作用的基本結构可能为一个含銻的螯合物分子中拥有以氮为中心而具有三个以上的羧甲基。     

Antitumor effect of avermectins

The effect of a mixture of naturally occurring aversectin C and avermectin B(1) on the growth of ascites and solid experimental tumors of mice was studied. It was shown for the first time that avermectins possess a pronounced antitumor action. When added at nontoxic doses, they significantly suppressed the growth of ascites Ehrlich carcinoma and P388 lympholeukemia and solid Ehrlich and 755 carcinomata. With some administration regimens, avermectins suppressed the tumor growth by 70-80%. Avermectins were most effective when injected intraperitoneally. It was also shown that avermectins enhanced the vincristine-induced suppression of the growth of Ehrlich carcinoma, melanoma B16, and P388 lympholeukemia. Avermectins produced this effect only when injected after vincristine.