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Mitochondrial-derived ROS in edelfosine-induced apoptosis in yeasts and tumor cells.
Acta Pharmacol Sin. 2007 Jun; 28(6):888-94.AP

Abstract

AIM

To investigate whether a similar process mediates cytotoxicity of 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3, edelfosine) in both yeasts and human tumor cells.

METHODS

A modified version of a previously described assay for the intracellular conversion of nitro blue tetrazolium to formazan by superoxide anion was used to measure the generation of reactive oxygen species (ROS). Apoptotic yeast cells were detected using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. DNA fragmentation and the generation of ROS were measured by cytofluorimetric analysis in Jurkat cells.

RESULTS

Edelfosine induced apoptosis in Saccharomyces cerevisiae, as assessed by TUNEL assay. Meanwhile, edelfosine induced a time- and concentration-dependent generation of ROS in yeasts. Rotenone, an inhibitor of the mitochondrial electron transport chain, prevented ROS generation and apoptosis in response to edelfosine in S cerevisiae. alpha-Tocopherol abrogated the edelfosine-induced generation of intracellular ROS and apoptosis. Edelfosine also induced an increase of ROS in human leukemic cells that preceded apoptosis. The overexpression of Bcl-2 by gene transfer abrogated both ROS generation and apoptosis induced by edelfosine in leukemic cells. Changes in the relative mitochondrial membrane potential were detected in both yeasts and Jurkat cells.

CONCLUSION

These results indicate that edelfosine induces apoptosis in yeasts in addition to human tumor cells, and this apoptotic process involves mitochondria, likely through mitochondrial-derived ROS. These data also suggest that yeasts can be used as a suitable cell model in elucidating the antitumor mechanism of action of edelfosine.

Authors+Show Affiliations

Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17506948

Citation

Zhang, Hui, et al. "Mitochondrial-derived ROS in Edelfosine-induced Apoptosis in Yeasts and Tumor Cells." Acta Pharmacologica Sinica, vol. 28, no. 6, 2007, pp. 888-94.
Zhang H, Gajate C, Yu LP, et al. Mitochondrial-derived ROS in edelfosine-induced apoptosis in yeasts and tumor cells. Acta Pharmacol Sin. 2007;28(6):888-94.
Zhang, H., Gajate, C., Yu, L. P., Fang, Y. X., & Mollinedo, F. (2007). Mitochondrial-derived ROS in edelfosine-induced apoptosis in yeasts and tumor cells. Acta Pharmacologica Sinica, 28(6), 888-94.
Zhang H, et al. Mitochondrial-derived ROS in Edelfosine-induced Apoptosis in Yeasts and Tumor Cells. Acta Pharmacol Sin. 2007;28(6):888-94. PubMed PMID: 17506948.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mitochondrial-derived ROS in edelfosine-induced apoptosis in yeasts and tumor cells. AU - Zhang,Hui, AU - Gajate,Consuelo, AU - Yu,Li-Ping, AU - Fang,Yun-Xiang, AU - Mollinedo,Faustino, PY - 2007/5/18/pubmed PY - 2009/4/21/medline PY - 2007/5/18/entrez SP - 888 EP - 94 JF - Acta pharmacologica Sinica JO - Acta Pharmacol Sin VL - 28 IS - 6 N2 - AIM: To investigate whether a similar process mediates cytotoxicity of 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3, edelfosine) in both yeasts and human tumor cells. METHODS: A modified version of a previously described assay for the intracellular conversion of nitro blue tetrazolium to formazan by superoxide anion was used to measure the generation of reactive oxygen species (ROS). Apoptotic yeast cells were detected using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. DNA fragmentation and the generation of ROS were measured by cytofluorimetric analysis in Jurkat cells. RESULTS: Edelfosine induced apoptosis in Saccharomyces cerevisiae, as assessed by TUNEL assay. Meanwhile, edelfosine induced a time- and concentration-dependent generation of ROS in yeasts. Rotenone, an inhibitor of the mitochondrial electron transport chain, prevented ROS generation and apoptosis in response to edelfosine in S cerevisiae. alpha-Tocopherol abrogated the edelfosine-induced generation of intracellular ROS and apoptosis. Edelfosine also induced an increase of ROS in human leukemic cells that preceded apoptosis. The overexpression of Bcl-2 by gene transfer abrogated both ROS generation and apoptosis induced by edelfosine in leukemic cells. Changes in the relative mitochondrial membrane potential were detected in both yeasts and Jurkat cells. CONCLUSION: These results indicate that edelfosine induces apoptosis in yeasts in addition to human tumor cells, and this apoptotic process involves mitochondria, likely through mitochondrial-derived ROS. These data also suggest that yeasts can be used as a suitable cell model in elucidating the antitumor mechanism of action of edelfosine. SN - 1671-4083 UR - https://www.unboundmedicine.com/medline/citation/17506948/Mitochondrial_derived_ROS_in_edelfosine_induced_apoptosis_in_yeasts_and_tumor_cells_ L2 - https://doi.org/10.1111/j.1745-7254.2007.00568.x DB - PRIME DP - Unbound Medicine ER -