Surgery, chemotherapy and radiotherapy, which are known as conventional cancer treatments, have been applied for more than 40 years. Because the target of chemotherapy is tumor cells, treatment ...agents are used at high doses during application and this creates toxic responses, causing side effects in normal cells. Furthermore, due to the high doses, cancer cells develop resistance to the agent and, as a result, success of the treatment gradually decreases. That is why chemotherapy is combined with various other cancer treatments to increase the therapeutic efficacy while reducing the side effects. In this study, the cytotoxic effect of endostatin, vinorelbine and their combination on breast cancer cell line MDAMB 231 was researched in vitro. In addition, the effects caused by the combination on TRAIL, TNF-α and caspase-2, 3, 6, 8 and -9 proteins, which undertake key roles in apoptosis were investigated. Cytotoxic effects of both agents and their combinations on normal epithelial cells (293 T) were also studied and compared. We found that endostatin is cytotoxic for cancer cells through caspase-8 and TNF-α activation, which affects the extrinsic pathway of apoptosis Combining endostatin as an anti-angiogenic agent with vinorelbine significantly suppressed the cytotoxicity that vinorelbine exerts on normal cells.
We aimed to determine the cytotoxic and immunomodulatory effects of hydroalcoholic extracts of the roots and aerial parts of Ebenus boissieri (EB) on breast cancer MDA-MB231 cells and the ...non-cancerous human embryonic kidney cell line, 293T. Cell viability was determined by MTT assay, trypan blue exclusion, and Live/Dead Viability/Cytotoxicity assay. Apoptosis was evaluated by measuring the activity of caspase-2, 3, 6, 8, and 9. Tumor necrosis factor (TNF)-α and interferon (IFN)-g release was assayed by ELISA, and protein expression of caspase-3, TNF-a, and IFN-g was determined by western blot. The results of this study revealed that MDA-MB231 cell viability was reduced in a dose-dependent manner by the aerial and root extract of EB at 72 h with a half-maximal inhibitory concentration (IC50) of 41.1 ± 2.76 and 65 ± 1.09 μg/mL, respectively. In contrast, neither the aerial nor the root extracts of this plant inhibited the proliferation of 293T cells at doses up to 1000 μg/mL. There was a time-dependent increase in caspase activity, especially caspase-3 and caspase-9. The levels of TNF-aand IFN-g significantly increased in MDA-MB231 cells treated with aerial extract. In conclusion, the extracts of EB induced apoptosis in breast cancer cells by altering the levels of caspases, TNF-a, and IFN-g. The components and precise modes of action of EB have not yet been determined. However, potential antitumor and immunomodulatory activity was observed along with selectivity against cancer cells in vitro, suggesting that hydroalcoholic extracts of this plant are worthy of additional study.
To evaluate protective effect of antioxidant enzymes against epirubicin-HCI (EPI) cytotoxicity in vitro.
Viability of MCF-7 cells treated with EPI was measured using the MTT test. Glutathione (GSH), ...protein content and enzymatic activity were measured spectrophotometrically. NADPH - dependent cytochrome P-450 reductase (NADPH-CYP-450) and glutathione S-transferase pi (GST-pi) expression in MCF-7 cells were determined by Western blot analysis.
The IC50 values of EPI in MCF-7 cells were 1.0, 0.7 and 0.5 ng/ml respectively for 24, 48 and 72 h applications. Simultaneously enzymatic activity of glutathione S-transferase, glutathione peroxidase, GSH and expression of GST-pi, NADPH-CYP-450 reductase were increased in EPI (1 ng/ml) - treated cells at the end of the 24 h incubation. Addition of superoxide dismutase, catalase and GSH decreased cytotoxicity of EPI.
We hypothesized that the production of reactive oxygen species and hydrogen peroxide as result of EPI treatment can cause cytotoxicity in MCF-7 cells and antioxidant enzymes protect the cells against this process.
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Background: Substance P (SP), a neuropeptide, is known to induce tumor cell proliferation. In contrast with intact peptide, the fragments of SP are suggested to inhibit the growth ...of various cancer cells. The aim of the present study was to determine cytotoxic effects of physiological fragments of SP either alone or in combination with radiotherapy on mouse breast cancer cells.
Methods: In this study, we tested the physiological fragments of SP such as SP (4-11), SP (6-11) and SP (1-7). Dose-response and time-course studies were carried out with various concentrations (100-0.001 nM) of SP fragments and the intact peptide. 4T1 mouse breast cancer cell lines were used in this study. The cytotoxic effect of SP fragments alone or in combination with radiotherapy was determined via WST-1 assay. Changes in substance P amounts in cells and in mediums determined by SP EIA kit.
Results: SP(4-11) and SP(6-11), but not SP(1-7), inhibited the proliferation of breast cancer cells and potentiated antitumor effects of radiotherapy. Moreover, the intact peptide alone did not alter the proliferation rate of 4T1 cells and the cytotoxic effects of the fragments were not inhibited by SP.
Conclusions: These results demonstrate that combined treatment with 2 fragments of SP (4-11 and 6-11) and radiotherapy induce cytotoxic effects. These data may provide the basis for a strategy, in which it is possible to use SP fragments and radiotherapy together to improve the efficiency of the independent therapies.
Accumulating evidence suggests the concept that epirubicin and lymphokine-activated killer (LAK) cells cytotoxicity may be mediated by free radicals generation and P-glycoprotein-positive (Pg-p+) ...cancer cells are more sensitive for LAK cells than their drug-sensitive parental lines. We tested this hypothesis further by exposing drug-sensitive (WT) and epirubicin-resistant MCF-7 human breast tumor cells to epirubicin and LAK cells. Subsequently, we monitored cell proliferation as a measure of cytotoxicity. The cytotoxicity of epirubicin, LAK, and LAK + epirubicin (1/10 of IC50) was evaluated in 400-fold epirubicin resistant MCF-7 EPI(R) (P-glycoprotein overexpressing) and drug-sensitive MCF-7 WT cells. IC50 values were measured using the MTT cytotoxicity test. The MCF-7 EPI(R) cells exhibited an increased susceptibility to LAK cells than did the MCF-7 WT cells. P-gp+ MCF-7 EPI(R) cells were lysed by human LAK cells to a greater extend than were their drug-sensitive counterparts. LAK + epirubicin combined treatment increased susceptibility of MCF-7 WT and MCF-7 EPI(R) cells to LAK cells cytotoxicity. For both cell lines, cytotoxicity was dependent upon the concentration of the epirubicin and effector cell/target cell (E/T) ratio. The resistance of MCF-7 EPI(R) cells to epirubicin appears to be associated with a developed tolerance to superoxide, most likely because of a tree-fold increase in superoxide dismutase (SOD) activity and 13-fold augmented selenium dependent glutathione peroxidase (GSH-Px) activity. Acting in concert, these two enzymes would decrease the formation of hydroxyl radical from reduced molecular oxygen intermediates. The addition of SOD decreased cytotoxicity of epirubicin and LAK cells. Taken together, these observations support the role of oxygen radicals in the cytotoxicity mechanism of epirubicin and suggest further that the development of resistance to this drug by the MCF-7 EPI(R) tumor cells may have a component linked to oxygen free radicals. It is proposed that production of reactive oxygen species by the treatment of epirubicin and LAK cells can cause cytotoxicity of MCF-7 WT and MCF-7 EPI(R) cells. SOD, catalase, GSH-Px, GST (glutathione S-transferase), and GSH (reduced glutathione) must be considered as part of the intracellular antioxidant defense mechanism of MCF-7 WT and MCF-7 EPI(R) cells against reactive oxygen species.
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EMUNI, FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UL, UM, UPUK, VKSCE, ZAGLJ
: Tissue injury resulting from ischemia‐reperfusion is of fundamental importance. Experimental evidence suggests that the generation of reactive oxygen species is significantly responsible for this ...type of injury. In the present study, besides investigating the protective role of melatonin on tissue damage caused by intestinal ischemia‐reperfusion, the protective activity of this compound was also analyzed in both pre‐ and post ischemia melatonin‐treated rats. The activities of the main antioxidative enzymes, catalase, superoxide dismutase and glutathione peroxidase in the intestine showed significant (P < 0.05) increases in melatonin‐treated animals that were subjected to ischemia/reperfusion compared with those subjected only to ischemia/reperfusion. Also, results clearly indicate that the level of malondialdeyhde, an index of lipid peroxidation, decreased significantly (P < 0.05) when rats subjected to intestinal/reperfusion were given melatonin either before ischemia or before reperfusion.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
In our study, the protective effects of vitamin E and Se (selenium) against cigarette smoke hazards on second-hand smoker (passive smoker) male mice (Balb/c) were investigated. Serum MDA levels in ...the smoke-exposed mice were found higher than serum MDA levels of control mice and Se- and vitamin E-treated mice. But, the MDA levels of smoke-exposed plus Se- and vitamin E-treated mice were found lower than MDA levels of smoke-exposed mice at the end of the three and five months. According to these results, application of vitamin E and Se, when given to smoke-exposed mice together, had an additive protective effect against cigarette smoke hazards (p < 0.05). Vitamin E also had protective effect on formation of 8-OHdG in smoke-exposed mice. The serum 8-OHdG amounts of smoke-exposed plus vitamin E-treated mice were found low, but the serum 8-OHdG amounts of smoke-exposed mice were found high. Also 8-OHdG levels in the serum of the smoke-exposed mice were increased which occurs as a result of DNA oxidation (p < 0.05). At the end of the three and five months, COMT (catechol-o-methyl transferase) activity of smoke-exposed mice livers were increased but, vitamin E and/or Se showed a significant protective effect on changing of COMT activity only at the end of the 5 months. Our results showed that MDA levels and 8-OHdG amounts were increased in the serum of smoke-exposed mice. On the other hand, vitamin E and Se had an additive protective effect against increasing MDA level. Also vitamin E had a protective effect against formation of 8-OHdG amounts and COMT activity alterations.
Callus induction and plant regeneration from mature embryos of different wheat genotypes Nasircilar, A.G. (Akdeniz Univ., Antalya (Turkey). Dept. of Biology); Turgut, K. (Akdeniz Univ., Antalya (Turkey). Dept. of Crop Fields); Fiskin, K. (Akdeniz Univ., Antalya (Turkey). Dept. of Biology)
Pakistan journal of botany,
(Sep 2006), Volume:
38, Issue:
3
Journal Article
Peer reviewed
Mature embryos of 5 Triticum aestivum and 5 T. durum cultivars formed embryogenic callus on two different media. Embryos were removed from surface sterilized seeds and placed with the scutellum ...upwards on a solid agar medium containing the inorganic components of Murashige & Skoog and 2 mg/L 2,4-dichlorophenoxyacetic acid (2,4-D) or 1 mg/L naphtalenacetic acid (NAA). The developed calli and regenerated plants were maintained on 2,4-D or NAA free MS medium. Wheat plants can be regenerated via two different systems. There were significant differences in percentage of callus induction and regeneration capacity on the different initiation medium. Among the T. aestivum cultivars, Yakar had the highest regeneration capacity in both induction mediums. In T durum cultivars, Kiziltan gave the highest regeneration capacity in MS + 2,4 D medium and Yilmaz gave the highest regeneration capacity in MS + NAA medium. A strong genotypic effect on the culture responses was found for both induction mediums.
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