AMPK Activation of Apoptotic Markers in Human Breast Cancer Cell Lines with Different p53 Backgrounds: MCF-7, MDA-MB-231 and T47D Cells

Document Type : Research Articles

Authors

1 Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Imam Abulrahman Bin Faisal University, 31441, Dammam, Saudi Arabia.

2 Department of Human Metabolism, The Medical School, University of Sheffield, Sheffield, S10 2RX, United Kingdom.

Abstract

Background: Downregulation of AMPK has been established as a major contributor to carcinogenesis in many types of human cancer. We sought to investigate the influence of activated AMPK on apoptotic markers in human breast cancer cells differing in their p53 status, as well as estrogen receptor status (MCF-7 (p53+ and ER+), MDA-MB-231 (p53 mutant and ER-) and T47D (p53 mutant and ER+)). Methods: We examined the effect of AICAR-activated AMPK on PARP cleavage, Bax redistribution, the involvement of intrinsic and extrinsic pathways of apoptosis using selective caspase inhibitors and cell cycle progression and p21 levels. Results: PARP cleavage occurred to a greater extent in MCF-7 and MDA-MB-231 cells, whereas Bax translocation was slower in MDA-MB-231 cells. Although there were quantitative differences in the effect of caspase inhibitors, it was clear that AMPK activation predominately affected the intrinsic pathway of apoptosis. Although, p21 was increased in all 3 cell types, there were quantitative and time differences. Apoptosis, as measured by fluorimetry, was increased in all three cell types. Conclusion: The impact of AMPK activation was cell type dependent resulting in differential activation of apoptotic markers, confirming that the genetic background of breast cancer may have an influence on the mode of action of AMPK. Thus, different anti-tumour mechanisms may be elicited depending on the cellular genotype.

Keywords

Asian Pacific Journal of Cancer Prevention
Volume 20, Issue 12
December 2019
Pages 3763-3770

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History

  • Receive Date: 27 August 2019
  • Revise Date: 13 November 2019
  • Accept Date: 02 December 2019

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