A novel N-alkylated prodigiosin analogue induced death in tumour cell through apoptosis or necrosis depending upon the cell type.
OBJECTIVE
To investigate the mechanism of cell death induced by the N-alkylated prodigiosin analogue, 2,2'-[3-methoxy-1'amyl-5'-methyl-4-(1''-pyrryl)] dipyrryl-methene (MAMPDM) in S-180 and EL-4 tumour cell lines.


METHODS
Effect of MAMPDM on cell viability was assessed by MTT dye conversion. Induction of apoptosis was assessed by monitoring caspase 3 activity using a fluorogenic substrate, fragmentation of DNA by gel electrophoresis and sub-diploid DNA containing cells by flowcytometry. Necrosis was estimated by flowcytometric analysis of the uptake of propidium iodide.


RESULTS
MAMPDM inhibited the proliferation of murine fibrosarcoma, S-180 cells and induced cell death. Investigations into the mechanism of cell death by MAMPDM in S-180 cells showed absence of hallmarks of apoptotic cell death such as activation of caspase 3, DNA fragmentation and presence of cells with sub-diploid DNA content. However, there was a rapid loss of membrane integrity as assessed by uptake of propidium iodide, which is characteristic of necrosis. In contrast to induction of necrosis in S-180 cells, MAMPDM induced apoptotic cell death in EL-4 cells as evident by activation of caspase 3, fragmentation of DNA and sub-diploid DNA containing cells.


CONCLUSIONS
MAMPDM could induce cell death by either apoptosis or necrosis depending upon the cell type. This would be of advantage in elimination of tumor cells defective in apoptotic pathway and therefore, refractory to the conventional therapies.
Deorukhkar
Amit A
AA
Food Technology Division, Bhabha Atomic Research Centre, Mumbai 400 085, India.
Chander
Ramesh
R
Pandey
Ruchi
R
Sainis
Krishna B
KB
D000475:Alkenes / Q000494:pharmacology*; D000478:Alkylation; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D003609:Dactinomycin / Q000494:pharmacology; D004171:Diploidy; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016399:Lymphoma, T-Cell / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D009336:Necrosis; D011353:Prodigiosin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D012510:Sarcoma 180 / Q000188:drug therapy; D019311:Staurosporine / Q000494:pharmacology; D013778:Tetrazolium Salts; D013844:Thiazoles
C477858:2,2'-(3-methoxy-1'amyl-5'-methyl-4-(1-pyrryl)) dipyrryl-methene; D000475:Alkenes; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D004791:Enzyme Inhibitors; D011758:Pyrroles; D013778:Tetrazolium Salts; D013844:Thiazoles; D003609:Dactinomycin; C022616:thiazolyl blue; D019311:Staurosporine; D011353:Prodigiosin