CYTOTOXIC AND APOPTOTIC FUNCTION OF CARMOFUR IN HEPATOCELLULAR CARCINOMA

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Apoptosis is a fundamental genetically controlled celldeath process that controls cell number by removal ofunwanted and potentially dangerous cells. Failure ofapoptosis can cause severe anomolies, ranging fromautoimmune disease to cancer. Despite of clinical treatments,hepatocelllular carcinoma is one of the mostcommon causes of liver cancer death. The main purposesof cancer treatment are to inhibit the proliferation andto induce the apoptosis of cancer cells. Recent studiesregarding the relationship between sphingolipids andcarcinogenesis are revealing novel molecular targets forcancer chemopreventation. We tested whether carmofur,a ceramidase inhibitör and a derivate of 5-fluorouracil,changes the survival rate and induces apoptosis in a humanhepatoma cell line (HepG2). We determined in vitrosurvival rate with MTT, apoptosis with flow cytometryand morphological changes with confogal microscopy. After treatment of hepotama cells with carmofur (5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55 ve 60 μM) for 24 h, cell survival rate was determined as 100, 77, 65, 64, 46, 38, 34, 30, 26, 20, 14 ve 9 %, compared to control group (% 100), respectively.Increased percentage of apoptotic cells aftertreatment of cells in this population with 24 μMcarmofur (the half maximal inhibitory concentration)for 24 h was determi-ned. The total death rate ofcontrol group ( 1 %) of hepo-toma cells was increased upto (28 %) after 24 hr carmofur treatment. Themorphological changes as apoptotic mar-kers wereobserved by confogal microscopy (chromatincondensation, cell shrinkage, fragmented DNA andcy-toskeleton and cell membrane misconfigurations).This study revealed that carmofur possesesantiproliferative and apoptotic properties on hepatoma cells.

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Carmofur , Apoptotic , Antiproliferative , Hepatoma

Kocatepe Medical Journal

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Kocatepe Medical Journal