Reciprocal modulation of histone deacetylase inhibitors sodium butyrate and trichostatin A on the energy metabolism of breast cancer cells.

Abstract:

:Tumor cells display different bioenergetic profiles when compared to normal cells. In the present work we showed metabolic reprogramming by means of inhibitors of histone deacetylase (HDACis), sodium butyrate and trichostatin A in breast cancer cells representing different stages of aggressiveness and metabolic profile. When testing the effect of NaB and TSA on viability of cells, it was shown that non-tumorigenic MCF-10A cells were less affected by increasing doses of the drugs than the tumorigenic, hormone dependent, tightly cohesive MCF-7, T-47D and the highly metastatic triple-negative MDA-MB 231 cells. T-47D cells were the most sensitive to treatment with both, NaB and TSA. Experiments measuring anchorage- independent growth of tumor cells showed that MCF-7, T-47D, and MDA-MB-231 cells were equally sensitive to the treatment with NaB. The NaB induced an attenuation of glycolysis, reflected by a decrease in lactate release in MCF-7 and T47D lines. Pyruvate kinase activity was significantly enhanced by NaB in MDA-MB-231 cells only. In contrast, the inhibitor enhanced lactate dehydrogenase activity specifically in T-47 D cells. Glucose-6-phosphate dehydrogenase activity was shown to be differentially modulated by NaB in the cell lines investigated: the enzyme was inhibited in MCF-7 cells, whereas in T-47D and MDA-MB-231 cells, G6PDH was activated. NaB and TSA were able to significantly increase the oxygen consumption by MDA-MB-231 and T-47D cells. Collectively the results show that epigenetic changes associated to acetylation of proteins in general affect the energy metabolism in all cancer cell lines and that mitochondria may occupy a central role in metastasis.

journal_name

J Cell Biochem

authors

Rodrigues MF,Carvalho É,Pezzuto P,Rumjanek FD,Amoêdo ND

doi

10.1002/jcb.25036

subject

Has Abstract

pub_date

2015-05-01 00:00:00

pages

797-808

issue

5

eissn

0730-2312

issn

1097-4644

journal_volume

116

pub_type

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