Browsing by Subject "Mitochondrial respiration"

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    Acquired tolerance of hepatocellular carcinoma cells to selenium deficiency: a selective survival mechanism?
    (American Association for Cancer Research, 2003) Irmak, M. B.; Ince, G.; Ozturk, M.; Cetin Atalay, R.
    Selenium is essential to human health, and its deficiency is associated with different diseases including liver necrosis. Selenium is protective against viral hepatitis and hepatocellular carcinoma (HCC). The underlying molecular mechanisms of selenium effects are not well known. In this study, in vitro response of HCC-derived cell lines to selenium deficiency is examined alone or in conjunction with Vitamin E and copper/zinc. Here, we show that itt vitro selenium deficiency in a subset of HCC-derived cell lines causes oxidative stress and cytochrome c release with subsequent cell death by apoptosis. The oxidative stress and consequent cell death induced by selenium deficiency on these cells are reverted by the antioxidant effect of Vitamin E. However, most HCC cell lines (10 of 13) tolerate selenium deficiency. Consequently, they escape apoptosis. Moreover, nine of these tolerant cell lines have integrated hepatitis B Virus (HBV) DNA in their genomes, and some display p53-249 mutation, indicating past exposure to HBV or aflatoxins, established factors for oxidative stress and cancer risk in liver. An HBV-transfected clone (2.2.15) of the sensitive HepG2 cell line has gained tolerance to selenium deficiency. Our findings indicate that selenium deficiency induces apoptosis in some "hepatocyte-like" cells. However, most HCC cells, particularly HBV-related ones, tolerate selenium deficiency and escape its deadly consequences. Thus, as demonstrated by the gain of survival capacity of apoptosis-sensitive cell lines with Vitamin E, such malignant cells have acquired a selective survival advantage that is prominent under selenium-deficient and oxidative-stress conditions.
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    ItemOpen Access
    ER-mitochondrial communication gets stressful
    (American Association for the Advancement of Science, 2014) Erbay, Ebru
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    Synthesis of new N,N′-bis [1-aryl-3-(piperidine-1-yl)propylidene] hydrazine dihydrochlorides and evaluation of their cytotoxicity against human hepatoma and breast cancer cells
    (Informa Healthcare, 2014) Kucukoglu, K.; Gul, H. I.; Cetin Atalay, R.; Baratli, Y.; Charles, A. L.; Sukuroglu, M.; Gul, M.; Geny, B.
    N,N0-Bis[1-aryl-3-(piperidine-1-yl)propylidene]hydrazine dihydrochlorides were synthesized by the reaction of 2 mols of 1-aryl-3-(piperidine-1-yl)-1- propanone hydrochlorides with 1 mol of hydrazine hydrate. Aryl part was C 6H5 (P1), 4-CH3C6H4 (P2), 4-CH3OC6H4 (P3), 4-HOC6H 4 (P4), 4-ClC6H4 (P5), 3-CH3OC 6H4 (P6), 4-FC6H4 (P7) and 4-BrC6H4 (P8). Except P1, all compounds were reported for the first time. The chemical structures were confirmed by UV, 1H NMR, 13C NMR and HRMS spectra. P1, P2, P7 and P8 against human hepatoma (Huh7) cells and P1, P2, P4, P5, P6, P7 and P8 against breast cancer (T47D) cells have shown cytotoxicity. P1, P2 and P7 had more potent cytotoxicity against Huh7 cells than the reference compound 5-FU, whereas only P2 was more potent than the 5-FU against T47D cells. Representative compound P7 inhibited the mitochondrial respiration at 144, 264 and 424 mM concentrations dose-dependantly in liver homogenates. The results suggest that P1, P2, P7 and P8 may serve as model compounds for further synthetic studies. © 2014 Informa UK Ltd.