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Apoptosis, autophagy, accelerated senescence and reactive oxygen in the response of human breast tumor cells to adriamycin.
Biochem Pharmacol. 2009 Apr 01; 77(7):1139-50.BP

Abstract

Although the primary response to Adriamycin (doxorubicin) in p53 mutant MDA-MB231 and p53 null MCF-7/E6 breast tumor cells is apoptotic cell death, the residual surviving population appears to be in a state of senescence, based on cell morphology, beta galactosidase staining, induction of p21(waf1/cip1) and down regulation of cdc2/cdk1. Suppression of apoptosis in MDA-MB231 and MCF-7/E6 cells treated with Adriamycin using the broad spectrum caspase inhibitor, zvad-Fmk, results in substantial induction of autophagy. Overall sensitivity to Adriamycin, measured by clonogenic survival, is not altered in the cells undergoing autophagy, consistent with autophagy contributing to cell death in response to Adriamycin. The free radical scavengers, glutathione and N-acetyl cysteine attenuate the accelerated senescence response to Adriamycin in MCF-7 cells as well as in MDA-MB231 and MCF-7/E6 cells, but protect primarily the MCF-7 cells, indicating that reactive oxygen is unlikely to be directly responsible for Adriamycin toxicity in breast tumor cells. Expression of caspase 3 or induced expression of c-myc in MCF-7 cells fails to abrogate accelerated senescence induced by Adriamycin. Taken together, these studies suggest that accelerated senescence induced by Adriamycin is similar in cells with wild type p53 and in cells lacking functional p53 with regard to the upregulation of p21(waf1/cip1), down regulation of cdc2 and the involvement of reactive oxygen species. Furthermore, accelerated senescence, autophagy and apoptosis all appear to be effective in suppressing self-renewal capacity in breast tumor cells exposed to Adriamycin.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, United States.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

19185564

Citation

Di, Xu, et al. "Apoptosis, Autophagy, Accelerated Senescence and Reactive Oxygen in the Response of Human Breast Tumor Cells to Adriamycin." Biochemical Pharmacology, vol. 77, no. 7, 2009, pp. 1139-50.
Di X, Shiu RP, Newsham IF, et al. Apoptosis, autophagy, accelerated senescence and reactive oxygen in the response of human breast tumor cells to adriamycin. Biochem Pharmacol. 2009;77(7):1139-50.
Di, X., Shiu, R. P., Newsham, I. F., & Gewirtz, D. A. (2009). Apoptosis, autophagy, accelerated senescence and reactive oxygen in the response of human breast tumor cells to adriamycin. Biochemical Pharmacology, 77(7), 1139-50. https://doi.org/10.1016/j.bcp.2008.12.016
Di X, et al. Apoptosis, Autophagy, Accelerated Senescence and Reactive Oxygen in the Response of Human Breast Tumor Cells to Adriamycin. Biochem Pharmacol. 2009 Apr 1;77(7):1139-50. PubMed PMID: 19185564.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Apoptosis, autophagy, accelerated senescence and reactive oxygen in the response of human breast tumor cells to adriamycin. AU - Di,Xu, AU - Shiu,Robert P, AU - Newsham,Irene F, AU - Gewirtz,David A, Y1 - 2009/01/06/ PY - 2008/09/12/received PY - 2008/12/12/revised PY - 2008/12/15/accepted PY - 2009/2/3/entrez PY - 2009/2/3/pubmed PY - 2009/4/10/medline SP - 1139 EP - 50 JF - Biochemical pharmacology JO - Biochem Pharmacol VL - 77 IS - 7 N2 - Although the primary response to Adriamycin (doxorubicin) in p53 mutant MDA-MB231 and p53 null MCF-7/E6 breast tumor cells is apoptotic cell death, the residual surviving population appears to be in a state of senescence, based on cell morphology, beta galactosidase staining, induction of p21(waf1/cip1) and down regulation of cdc2/cdk1. Suppression of apoptosis in MDA-MB231 and MCF-7/E6 cells treated with Adriamycin using the broad spectrum caspase inhibitor, zvad-Fmk, results in substantial induction of autophagy. Overall sensitivity to Adriamycin, measured by clonogenic survival, is not altered in the cells undergoing autophagy, consistent with autophagy contributing to cell death in response to Adriamycin. The free radical scavengers, glutathione and N-acetyl cysteine attenuate the accelerated senescence response to Adriamycin in MCF-7 cells as well as in MDA-MB231 and MCF-7/E6 cells, but protect primarily the MCF-7 cells, indicating that reactive oxygen is unlikely to be directly responsible for Adriamycin toxicity in breast tumor cells. Expression of caspase 3 or induced expression of c-myc in MCF-7 cells fails to abrogate accelerated senescence induced by Adriamycin. Taken together, these studies suggest that accelerated senescence induced by Adriamycin is similar in cells with wild type p53 and in cells lacking functional p53 with regard to the upregulation of p21(waf1/cip1), down regulation of cdc2 and the involvement of reactive oxygen species. Furthermore, accelerated senescence, autophagy and apoptosis all appear to be effective in suppressing self-renewal capacity in breast tumor cells exposed to Adriamycin. SN - 1873-2968 UR - https://www.unboundmedicine.com/medline/citation/19185564/Apoptosis_autophagy_accelerated_senescence_and_reactive_oxygen_in_the_response_of_human_breast_tumor_cells_to_adriamycin_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-2952(08)00895-2 DB - PRIME DP - Unbound Medicine ER -