prodigiosin and Carcinoma--Small-Cell

In the present study, we describe the cytotoxicity of the new drug prodigiosin (PG) in two small cell lung carcinoma (SCLC) cell lines, GLC4 and its derived doxorubicin-resistant GLC4/ADR cell line, which overexpresses multidrug-related protein 1 (MRP-1). We observed through Western blot that PG mediated cytochrome c release, caspase cascade activation and PARP cleavage, thereby leading to apoptosis in a dose-response manner. MRP-1 expression increased after PG treatment, although that does not lead to protein accumulation. The MTT assay showed no difference in sensitivity to PG between the two cell lines. Our results support PG as a potential drug for the treatment of lung cancer as it overcomes the multidrug resistance phenotype produced by MRP-1 overexpression.

Topics: Anti-Bacterial Agents; Antibiotics, Antineoplastic; Apoptosis; ATP Binding Cassette Transporter, Subfamily B, Member 1; Carcinoma, Small Cell; Caspases; Cytochromes c; Doxorubicin; Drug Resistance, Neoplasm; Enzyme Activation; Humans; Lung Neoplasms; Poly(ADP-ribose) Polymerases; Prodigiosin; Tumor Cells, Cultured

Prodigiosin (PG) is a secondary metabolite, isolated from a culture of Serratia marcescens, which has shown potent cytotoxicity against various human cancer cell lines as well as immunosuppressive activity. The purpose of this study was to evaluate the role of mitochondria in PG-induced apoptosis. Therefore, we evaluated the apoptotic action of PG in GLC4 small cell lung cancer cell line by Hoechst 33342 staining. In these cells, we examined mitochondrial apoptosis-inducing factor (AIF) and cytochrome c (cyt c) release to the cytosol in PG time-response studies. These findings suggest that PG induces apoptosis in both caspase-dependent and caspase-independent pathways.

Topics: Apoptosis; Carcinoma, Small Cell; Cell Line, Tumor; Cytochromes c; Humans; Lung Neoplasms; Microscopy, Fluorescence; Mitochondria; Prodigiosin