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首页> 外文期刊>Life sciences >Non-apoptotic concentrations of prodigiosin (H+/Cl- symporter) inhibit the acidification of lysosomes and induce cell cycle blockage in colon cancer cells
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Non-apoptotic concentrations of prodigiosin (H+/Cl- symporter) inhibit the acidification of lysosomes and induce cell cycle blockage in colon cancer cells

机译：非凋亡浓度的prodigiosin（H + / Cl-转运蛋白）抑制溶酶体的酸化并诱导结肠癌细胞的细胞周期阻滞

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摘要

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. (c) 2005 Elsevier Inc. All rights reserved.
机译：Prodigiosin（PG）是一种细菌红色素，具有有趣的免疫抑制和凋亡特性，部分归因于其通过促进H + / Cl-转运蛋白使V-ATPase偶联的能力。在本研究中，我们调查了非凋亡浓度的PG对溶酶体pH值和结肠癌细胞中细胞周期进程的影响。使用a啶橙活力染色法在DLD-1细胞中测试了溶酶体pH。橙色颗粒（表示酸化的溶酶体）在用25 nM PG处理1/2小时的细胞中显着下降，并在100 nM时完全消失。这表明PG可以诱导溶酶体碱化，而没有任何明显的细胞毒性作用。在HT29细胞中分析了细胞周期进程，我们发现PG诱导了G1期的阻滞。这种阻断与p21（WAF1 / CIP1）的诱导有关，可以依赖于或独立于p53触发。总之，结肠癌细胞中非凋亡浓度的PG诱导的溶酶体pH和细胞溶质酸化的可逆性增加，提示PG诱导的凋亡过程不能仅通过细胞内pH的变化来解释。必须更准确地分析细胞内酸化对细胞周期停滞的影响。 （c）2005 Elsevier Inc.保留所有权利。

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