الفهرس 
cancer
Oxidative stress and cancerOnly 14 pages are availabe for public view
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Abstract
Therapeutic selectivity, or preferential killing of cancer cells without significant toxicity to normal cells, is one of the most important considerations in cancer chemotherapy. Understanding the biological differences between normal and cancer cells is essential for the design and development of anticancer drugs with selective anticancer activity. Most cancer cells exhibit increased glycolysis and use this metabolic pathway for generation of ATP as a main source of their energy supply. This phenomenon is known as the Warburg effect and is considered as one of the most fundamental metabolic alterations during malignant transformation. The Warburg effect (aerobic glycolysis) has attracted much attention for its function in the tumorigenesis. Lactate dehydrogenase A (LDH-A) executes the final step of aerobic glycolysis and has been reported to be involved in the tumor progression. Lactate dehydrogenase-A (LDH-A) is the enzyme that converts pyruvate to lactate and oxidizes the reduced form of nicotinamide adenine dinucleotide to NAD+. Several human cancers display elevated expression of LDH-A. Because of its essential role in cancer metabolism, LDH-A has been considered to be a potential target for cancer therapy. Taxol is one of the most effective chemotherapeutic agents for the treatment of patients with breast cancer. Despite impressive clinical responses initially, the majority of patients eventually develop resistance to Taxol. Lactate dehydrogenase-A (LDH-A) is one of the predominant isoforms of LDH expressed in breast tissue. LDH-A plays an important role in Taxol resistance and inhibition of LDH-A re-sensitizes Taxol-resistant cells to Taxol. Therefore, the present study aimed to firstly investigate the potential anticancer effect of LDH inhibitors such as oxamate in Solid Ehrlich Carcinoma (SEC) model in mice and to clarify the molecular mechanisms involved in any potential therapeutic effects. Furthermore, this study investigated the effectiveness of oxamate in terms of potentiating the anti-tumor action of paclitaxel to ascertain if oxamate could be used as an adjuvant therapy in cancer treatment. Secondly, it also aimed to investigate the potential anticancer effect of oxamate and galloflavin as LDH inhibitors in different breast and ovarian cancer cell lines, in vitro. To achieve these objectives, firstly, a model of solid Ehrlich carcinoma (SEC) was induced in female Swiss albino mice, where 0.2 ml viable EAC cells (2x106/ ml) were implanted subcutaneously (S.C.) into the right thigh of the lower limb of mice. Treatment of oxamate or its control vehicle is initiated on day seven after implantation of EAC cells for 21 days on the basis of daily administrations. However, paclitaxel was I.P. injected on days 7th, 11th, 15th and 19th after tumor implantation.