Non-apoptotic concentrations of prodigiosin (H+/Cl- symporter) inhibit the acidification of lysosomes and induce cell cycle blockage in colon cancer cells.
Prodigiosin (PG) is a bacterial red pigment with interesting immunosuppressive and apoptotic properties that have been partly attributed to its ability to uncouple V-ATPase through the promotion of the H+/Cl- symporter. In the present study, we investigate the effect of non-apoptotic concentrations of PG on the lysosomal-pH and on cell cycle progression in colon cancer cells. Lysosomal-pH was tested in DLD-1 cells using acridine orange vital staining. Orange granules, indicative of acidified lysosomes, decreased significantly in cells treated with 25 nM of PG for 1/2 h, and disappeared completely at 100 nM. This suggests that PG can induce lysosomal alkalinization without any apparent cytotoxic effect. Cell cycle progression was analysed in HT29 cells and we found that PG induces a blockage in the G1 phase. This blockage correlates with p21(WAF1/CIP1) induction, and it can be triggered either dependently or independently of p53. In conclusion, the reversible increase in lysosomal-pH and cytosol acidification induced by non-apoptotic concentrations of PG in colon cancer cells, suggests that the apoptotic process induced by PG can not be solely explained by changes in intracellular pH. The effect of intracellular acidification on cell cycle arrest must be analysed more exactly.
Castillo-Avila
Wilmar
W
Department of Pathology and Experimental Therapy, CCBR Group, Pavelló Central, 5a planta, LR 5101 C/ Feixa Llarga s/n, E-08907, L'Hospitalet (Barcelona), Spain.
Abal
Miguel
M
Robine
Sylvie
S
Pérez-Tomás
Ricardo
R
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology*; D000970:Antineoplastic Agents; D017920:Antiporters / Q000037:antagonists & inhibitors*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D016193:G1 Phase / Q000187:drug effects; D016158:Genes, p53 / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008247:Lysosomes / Q000737:chemistry* / Q000187:drug effects*; D008856:Microscopy, Fluorescence; D011353:Prodigiosin / Q000494:pharmacology*
D000970:Antineoplastic Agents; D017920:Antiporters; C114260:hydrogen-chloride symporter; D011353:Prodigiosin