Percentage Increase In Life Span Research Articles

Synthesis and antitumor activity of new sulfonamide derivatives of thiadiazolo[3,2- a]pyrimidines

New series of sulfonamide derivatives of [1,3,4]thiadiazolo[3,2- a]pyrimidine were synthesized and investigated as antitumor agents. Some of the newly prepared compounds were tested for their in vitro and in vivo antitumor activities. Preliminary biological studies revealed that compounds 4c, 4f, and 4j exhibited the highest affinity to DNA, while compounds 4h, i, 6a– c, 8 and 12– 14 exhibited moderate activity. Also, compounds 4j, 4f and 4c showed the highest percentage increase in lifespan of mice inoculated with Ehrlich ascites cells over 5-flurouracil (positive control). The detailed synthesis, spectroscopic and biological data are reported.

Niosomal Entrapment of Hydroxypropyl‐β‐cylodextrin‐Methotrexate Complex as a Drug Delivery Device

An inclusion complex of methotrexate with hydroxypropyl-β-cylodextrin (HPβCyD) was prepared with a view to increase entrapment efficiency and thereby improve the anticancer activity and stability of the drug. The complex and the plain drug were entrapped in the niosomes using cholesterol, Span 60 and dicetyl phosphate. The niosomal entrapment efficiency was higher (89%) in the case of the drug-complex than with the plain drug (67%). When administered to tumour-bearing BALB/c mice at a dose of 5 mg kg−1, the complex entrapped in the niosomes produced a higher percentage increase in life span. Better stability on storage was also observed with the niosome-entrapped complex. Thus complexation of methotrexate with HPβCyD increases the efficiency of entrapment in nonionic surfactant vesicles and the entrapped complex is stable and has improved anticancer activity.

Study of the antitumor potential of Bidens pilosa (Asteraceae) used in Brazilian folk medicine

Aim of the study Bidens pilosa (L.) (Asteraceae) is a medicinal plant traditionally used in Brazil for treating conditions that can be related to cancer. Therefore the present study was carried out to evaluate the antitumor activity of extracts obtained from the aerial parts of this plant species. Materials and Methods The crude hydroalcoholic extract (HAE) (water:alcohol, 6:4) and solvent fractions (chloroform = CHCl 3 ,ethyl acetate = EtOAc, methanol = MeOH) were assessed for cytotoxicity assay by the brine shrimp and hemolytic, MTT and NRU assays. The antiproliferative potential of the crude extract and fractions was investigated in vivo using the Ehrlich ascites carcinoma (EAC) in isogenic Balb/c mice that were administered intraperitoneally 150 and 300 mg/kg body weight per day for nine days beginning 24 h after tumor inoculation. Results In in vitro cytotoxicity using Ehrlich ascites carcinoma cell line assay CHCl 3 extract proved to be more toxic than the crude HAE with an IC 50 of 97 ± 7.2 and 83 ± 5.2 μg/mL to NRU and MTT, respectively. Histomorphological evaluations indicated that the treatment with CHCl 3 and HAE extracts significantly reduced ( P < 0.05) body weight, abdominal circumference, tumor volume, packed cell volume and viable cell count, when compared to EAC control group. Furthermore, nonviable tumor cell count increased significantly ( P < 0.01) only under treatment with CHCl 3 or HAE, and this was accompanied by a marked percentage increase in life span (54.2 and 41.7%, respectively). Biochemical assays revealed that CHCl 3 and HAE extracts were also able to decrease serum LDH activity (39.5 and 30.6%) and GSH concentration (94.6 and 50.7%) in ascitic fluid, respectively. Conclusion The chloroform fraction showed the best and methanolic the worst antitumor activity.

Activation of Cytotoxic T Lymphocyte Responses and Attenuation of Tumor Growth in vivo by Andrographis paniculata Extract and Andrographolide

The stimulatory effect of Andrographis paniculata extract and andrographolide on cytotoxic T lymphocyte (CTL) production was determined in BALB/c mice by Winn's neutralization assay using CTL sensitive EL4 thymoma cells as target cell. Extract and andrographolide showed a significant increase in CTL production in both the in vivo and in vitro models. The survival time of EL4 cells alone in animals was only 27.1 days and it was increased to 51.1 and 44.5 days in extract- and andrographolide treated animals with percentage increase in life span (%ILS) of 88.5 and 64.2, respectively. The survival rate of animals administered EL4 cells incubated with alloimmunized spleen cells (effector cells) from normal BALB/c mice was 35.8 (%ILS 32.1). When this group was treated with 10 doses of extract and andrographolide the life span was further increased to 52.1 days (%ILS 92.2) and 48.1 days (%ILS 77.4). Survival days of animal carrying EL4 cells incubated with alloimmunized spleen cells (effector cells) from extract and andrographolide treated animals were 55.5 and 50.3 days respectively. When these animals continued with extract and andrographolide treatment for 10 days their life spans were significantly increased to 62 and 53.8 days, respectively. The level of cytokines such as Interlevkin (IL)-2 and Interferon (IFN)-γ also was enhanced in these animals when they were treated with extract and andrographolide. This study demonstrated that A. paniculata extract and andrographolide stimulate the CTL production through enhanced secretion of IL-2 and IFN-γ by T cells and thereby inhibit the tumor growth.

Proapoptotic and antitumor activities of the HMG-CoA reductase inhibitor, lovastatin, against Dalton's Lymphoma Ascites tumor in mice

Background Diet rich in fat have a clear effect on the tumor incidence in humans. Increased level of lipid peroxidation were found in colon, liver, breast and kidney carcinogenesis. Although the beneficial effects of statins for cardiovascular diseases are well established, their importance in the area of cancer therapeutics has recently gained recognition. Many studies of lovastatin in in vitro systems and experimental animals have been reported as an effective antitumor agent. However, phase I/II clinical trials in cancer patients demonstrated a minor to non-significant responses. Hence more studies in different tumor models using doses corresponding to that used to reduce lipid in human are required to support the antitumor activity. Methods The antitumor activity was evaluated using Daltons' Lymphoma Ascites (DLA) cell line-induced ascites tumor model in mice. Proapoptotic activity was evaluated in DLA cell line induced ascites animals after the treatment of lovastatin. Apoptosis was analyzed morphologically by staining with Giemsa and biochemically by observing the laddering of DNA in agarose gel electrophoresis. In vitro cytotoxic activity of lovastatin was studied by trypan blue dye exclusion method. Lipid peroxidation inhibiting activity was demonstrated in Fe 2+-ascorbate induced rat whole liver homogenate. Results Lovastatin dose dependently inhibited the ascites tumor growth at 4 and 16 mg/kg body wt (p.o). The percentage increase in life span (%ILS) in the 16 mg/kg treated group was 61.8% ( P < 0.01). Single dose of lovastatin (16 mg/kg body wt, p.o) was also effective to accelerate the apoptosis in the ascites tumor bearing mice that was evident from the multiple fragmentation of DNA in gel electrophoresis. Further the morphological analysis of DLA cells aspirated from the lovastatin treated animals showed a significant ( P < 0.01) increase of apoptotic cells (15.5 ± 3%) than the control animals (6.5 ± 1%). Concentration of lovastatin required for the 50% of the cytotoxicity was 37 ± 5 μg/ml. Lovastatin at its low concentrations were effective to inhibit lipid peroxidation. Conclusions The antitumor activity of lovastatin against the ascites tumor is due to its proapoptotic and cytotoxic activities. Lovastatin at low concentrations inhibited Fe 2+ induced lipid peroxidation in in vitro system. The proapoptotic and lipid peroxidation inhibiting activities of the lipid lowering drug lovastatin may further suggest its possible therapeutic use as a cancer chemopreventive agent.

Antitumor activity of total alkaloid fraction of solanum pseudocapsicum leaves.

The total alkaloid fraction of the methanolic extract of Solanum pseudocapsicum leaves was tested for its in-vivo antitumor activity against Dalton's Lymphoma Ascites model in mice. The total alkaloid fraction at 2.5 and 5.0 mg/kg body weight doses exhibited antitumor activity as revealed by the significant increase in the mean survival time and the percentage increase in life span of tumor bearing mice. The antitumor activity observed may be due to its cytotoxic properties. However the treatment caused a significant decrease in the body weight below the normal indicating the toxicity of the treatment.

Potentiation of adriamycin cytotoxicity in P388 murine leukemia sensitive and resistant to adriamycin by use of lonidamine and hyperthermia.

The in vitro effect of adriamycin (ADR) and lonidamine alone and in combination, at 37 degrees C and 43 degrees C, was investigated on murine leukemia P388 sensitive (P388/S) and resistant (P388/ADR) to adriamycin. The sensitive and the resistant cells were exposed in vitro with and without the drugs for 1 h at 37 degrees C and 43 degrees C. These cells were inoculated ip (10(6) cells/mouse) into groups of BDF1 mice. Cytotoxic effect of the treatment was assessed on the basis of percentage increase in life span (% ILS) of these animals, compared to the animals receiving cells which did not receive any treatment but exposed only to 37 degrees C for 1 h. It was observed that exposure of P388/ADR cells to lonidamine or adriamycin alone at 43 degrees C for 1 h resulted in greater cell kill, thus enhancing the % ILS of the experimental animals receiving those cells, compared to that of mice receiving the cells exposed to the same drugs for 1 h at 37 degrees C. However, the combination of lonidamine (0.02 mM) and adriamycin (10 micrograms/ml) at 43 degrees C for 1 h showed more than a synergistic effect, resulting in a % ILS of 120. Similar results were seen in the case of P388/S; however, the observations pertaining to P388/ADR are encouraging, since the mode of treatment has reversed the acquired resistance of P388 leukemia cells to adriamycin.

Etoposide prior to cis-diamminedichloroplatinum in combination chemotherapy: in vitro and in vivo studies

Antitumor effect and toxicity of etoposide (VP 16) in combination with cis-diamminedichloroplatinum (DDP) were studied on the in vitro C 108 line and its in vivo counterpart, the M 1087 line, both deriving from Lewis lung carcinoma. A colony-forming assay was used to assess the in vitro cytoxicity of each drug and, on the basis of survival curve shape indications, different drug sequences were analyzed in order to find the optimal combination. Tumor growth inhibition, growth delay, metastasis reduction and percentage increase in lifespan were considered as parameters of therapeutic effect. From the present work it can be derived that the VP 16-DDP combination produces a poor antitumour effect against the Lewis lung carcinoma lines, otherwise associated with a highly acute toxicity. The sequence in which VP 16 is given before DDP induces a significant antimetastatic effect together with acceptable toxicity.

Effectiveness of clinically active antineoplastic drugs in a surgical-adjuvant chemotherapy treatment regimen using the Lewis Lung (LL) carcinoma.

AbstractSurgical‐adjuvant chemotherapy studies were done with BDF1 mice bearing Lewis Lung (LL) carcinoma implanted intramuscularly (IM). Ten days (D10) after implantation, the tumor‐bearing leg was surgically amputated, and intraperitoneal (IP) drug treatment was started either 3 or 5 days after surgery using single‐dose therapy or intermittent treatment given every 4 days for three doses or daily treatment for five doses. The percentage increase in life span (%ILS) was used as the primary measure for evaluation. Data for 17 clinically active drugs showed that surgical‐adjuvant, single‐agent chemotherapy was markedly effective (%ILS&gt;100) in prolonging the life span of tumor‐bearing animals given BCNU, MeCCNU, and cytoxan; moderate activity (%ILS, 40–100) was obtained with bleomycin and vincristine, and marginal activity (%ILS, 35–40) was observed with 5‐fluorouracil (5‐FU), hexamethylmelamine (HMM), procarbazine, and dibromodulcitol. Surgical‐adjuvant, two‐drug‐combination chemotherapy treatment with bleomycin plus MeCCNU or cis‐platinum [cis‐PT(II)] plus CCNU were more effective than single‐drug chemotherapy in prolonging the life span of tumor‐bearing animals. When used in a surgical‐adjuvant chemotherapy‐treatment schedule, the solid tumor model was found to be sensitive to certain antineoplastic drugs that are of clinical benefit in the treatment of human lung cancer. Thus, the model is potentially useful in the search for newer single agents and combinations of drugs against cancers.