In spite of tremendous effort for improved
therapy,
lung cancer remains the leading cause of
cancer-related deaths worldwide. In the present study, we used the novel
purine ribunocleoside
sulfinosine and evaluated its antiproliferative and apoptotic outcome on the
non-small cell lung carcinoma cell line (NSCLC) and the
small cell lung carcinoma cell line (SCLC). Using a
BrdU incorporation-test
sulfinosine inhibited cell growth in a dose dependent-manner. ID50 values were 4.65 +/- 0.17 microM in the case of NSCLC cells, and 3.59 +/- 0.81 microM in the case of SCLC cells. MTT testing revealed that IC50 values were 6.24 +/- 0.77 microM for NSCLC and 5.68 +/- 0.58 microM for SCLC. Inhibitory concentrations (IC50 and ID50) for
sulfinosine were nonsignificantly lower in SCLC cells compared to NSCLC cells, indicating similar susceptibility of the cells. Flow-cytometric analysis, TUNEL staining,
DNA laddering and cell death ELISA test were used to investigate apoptotic cell death. Our results demonstrated that high concentrations of
sulfinosine can cause typical
DNA laddering, a hallmark for apoptosis. Evidence of free
nucleosomes and enzymatic labeling of fragmented
DNA confirmed apoptosis involvement in
sulfinosine cytotoxicity. In addition, flow-cytometric analysis showed that 25 microM
sulfinosine arrested cell cycle progression at the G2M phase and induction of apoptosis in both cell lines. From these results, we concluded that
sulfinosine may act as an
anticancer agent and further studies may prove its efficacy in
lung cancer cells. Thus the
biological effects of
sulfinosine may be due to modulation of cell growth, cell death, and cell cycle regulatory molecules.