Sulfinosine-induced cell growth inhibition and apoptosis in human lung carcinomas in vitro.
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.
Department of Neurobiology and Immunology, Institute for Biological Research, Belgrade, Serbia, Yugoslavia.
Javorina
J
Milosević
Selma
S
Kanazir
Ljubica
L
Medić-Mijacević
Vjera
V
Pejanović
Zdenka
Z
Stokić
Gordana
G
Konjević
Ljubisa
L
Rakić
Sabera
S
Ruzdijić
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001973:Bromodeoxyuridine; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004273:DNA, Neoplasm / Q000302:isolation & purification; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D008175:Lung Neoplasms / Q000473:pathology*; D011684:Purine Nucleosides / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014343:Trypan Blue; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D011684:Purine Nucleosides; D013778:Tetrazolium Salts; D013844:Thiazoles; C063871:sulfinosine; C022616:thiazolyl blue; D001973:Bromodeoxyuridine; D014343:Trypan Blue