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Sulfinosine-Induced Cell Growth Inhibition and Apoptosis in Human Lung Carcinomas In Vitro

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Abstract

In spite of tremendous effort for improvedtherapy, lung cancer remains the leadingcause of cancer-related deaths worldwide.In the present study, we used the novelpurine ribunocleoside sulfinosine andevaluated its antiproliferative andapoptotic outcome on the non-small celllung carcinoma cell line (NSCLC) and thesmall cell lung carcinoma cell line (SCLC).Using a BrdU incorporation-test sulfinosineinhibited cell growth in a dosedependent-manner. ID50 values were4.65 ± 0.17 μM in the case of NSCLCcells, and 3.59 ± 0.81 μM in thecase of SCLC cells. MTT testing revealedthat IC50 values were 6.24 ±0.77 μM for NSCLC and 5.68 ±0.58 μM for SCLC. Inhibitoryconcentrations (IC50 and ID50)for sulfinosine were nonsignificantly lowerin SCLC cells compared to NSCLC cells,indicating similar susceptibility of thecells. Flow-cytometric analysis, TUNELstaining, DNA laddering and cell deathELISA test were used to investigateapoptotic cell death. Our resultsdemonstrated that high concentrations ofsulfinosine can cause typical DNAladdering, a hallmark for apoptosis.Evidence of free nucleosomes and enzymaticlabeling of fragmented DNA confirmedapoptosis involvement in sulfinosinecytotoxicity. In addition, flow-cytometricanalysis showed that 25 μM sulfinosinearrested cell cycle progression atthe G2M phase and induction ofapoptosis in both cell lines. From theseresults, we concluded that sulfinosine mayact as an anticancer agent and furtherstudies may prove its efficacy in lungcancer cells. Thus the biological effectsof sulfinosine may be due to modulation ofcell growth, cell death, and cell cycleregulatory molecules.

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Authors and Affiliations

  1. Department of Neurobiology and Immunology, Institute for Biological Research, Serbia, Yugoslavia

    Javorina Milošević, Selma Kanazir, Ljubiša Rakić & Sabera Ruždijić

  2. ICN-Galenika, R&D, Batajnicki put bb, Serbia, Yugoslavia

    Ljubica Medić-Mijačević, Vjera Pejanović & Zdenka Stokić

  3. Institute of Oncology and Radiology of Serbia, Belgrade, Serbia, Yugoslavia

    Gordana Konjević

Authors
  1. Javorina Milošević
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  2. Selma Kanazir
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  3. Ljubica Medić-Mijačević
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  4. Vjera Pejanović
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  5. Zdenka Stokić
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  6. Gordana Konjević
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  7. Ljubiša Rakić
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  8. Sabera Ruždijić
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Milošević, J., Kanazir, S., Medić-Mijačević, L. et al. Sulfinosine-Induced Cell Growth Inhibition and Apoptosis in Human Lung Carcinomas In Vitro . Invest New Drugs 20, 229–240 (2002). https://doi.org/10.1023/A:1016281109100

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