Reactive oxygen species and mitochondrial membrane potential are modulated during CDDP-induced apoptosis in EC-109 cells

Authors: Cai, Xian-Bin; Hu, Hui; Chen, Su-Zuan; Chen, Bin-Ming; Cai, Ju-Yu; Jing, Xu-Bin

Source: Biochemistry and Cell Biology, Volume 85, Number 2, April 2007 , pp. 265-271(7)

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Abstract:

cis-Diamminedichloroplatinum (CDDP), commonly know as cisplatin, is a well known DNA-damaging agent, which is highly active in suppressing the proliferation of tumor cells. However, it is not clear that CDDP can induce growth inhibition of esophagus cancer cells. Using the cell line EC-109 from the esophagus, we found that CDDP would induce apoptotic responses. The addition of CDDP to cells led to the inhibition of growth in a time- and dose-dependent manner. CDDP generated reactive oxygen species (ROSs) in cells, which brought about a reduction in the intracellular mitochondrial transmembrane potential (Δψm), leading to apoptosis. Our findings demonstrate that ROSs, and the resulting oxidative stress, play a pivotal role in apoptosis. Preincubation of EC-109 cells with the hydrogen-peroxide-scavenging enzyme catalase partially inhibited the following: (i) the production of ROS; (ii) the disruption of the Δψm; and (iii) apoptosis. These results indicate that the enhancement of the generation of ROS and the disruption of Δψm are events involved in the apoptotic pathway of EC-109 induced by CDDP.

Le cis-diaminedichloroplatine (CDDP), communément appelé cisplatine, est un agent endommageant l'ADN bien connu, capable d'inhiber efficacement la prolifération de cellules tumorales. On ignore cependant si le CDDP peut causer l'inhibition de la croissance de cellules cancéreuses œsophagiennes. À l'aide de la lignée EC-109 provenant de l'œsophage, nous avons trouvé que le CDDP pouvait induire des réponses reliées à l'apoptose. L'ajout de CDDP aux cellules a causé une inhibition de la croissance de façon dépendante du temps et de la concentration. Le CDDP a généré des espèces réactives d'oxygène (ROS) cellulaires, ce qui a conduit à une réduction du potentiel membranaire mitochondrial intracellulaire (Δψm) et à l'apoptose. Nos résultats démontrent que les ROS et le stress oxydatif associé jouent un rôle clé dans l'apoptose. La pré-incubation de cellules EC-109 avec la catalase, une enzyme piégeant le peroxyde d'hydrogène, inhibait partiellement (i) la production de ROS; (ii) la dissipation du Δψm; et (iii) l'apoptose. Ces résultats indiquent que l'augmentation de la production de ROS et la dissipation du Δψm sont des événements impliqués dans la voie de l'apoptose des EC-109 induite par le CDDP.

Document Type: Research article

Publication date: 2007-04-01

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Reactive oxygen species and mitochondrial membrane potential are modulated during CDDP-induced apoptosis in EC-109 cells

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