期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/ijms23052645
关键词
breast cancer; MCF-7; HDAC8; VPA; metabolomics analysis
资金
- Instituto Politecnico Nacional (SIP),
- BEIFI
- COFAA-IPN [CB-254600, CB-241339, CB-284243]
- SEP-CONACYT-ANUIES-ECOS Francia [296636]
Research has found that valproic acid (VPA), a well-known histone deacetylase inhibitor (HDACi), can induce cell death in breast cancer cells by altering metabolic pathways. This includes metabolites that reduce cell proliferation and growth, interfere with energy sources, and increase reactive oxygen species levels. These findings suggest that VPA has different pharmacological mechanisms in killing cancer cells, and metabolomic approaches are a valuable source of information for understanding these mechanisms.
To target breast cancer (BC), epigenetic modulation could be a promising therapy strategy due to its role in the genesis, growth, and metastases of BC. Valproic acid (VPA) is a well-known histone deacetylase inhibitor (HDACi), which due to its epigenetic focus needs to be studied in depth to understand the effects it might elicit in BC cells. The aim of this work is to contribute to exploring the complete pharmacological mechanism of VPA in killing cancer cells using MCF-7. LC-MS/MS metabolomics studies were applied to MCF-7 treated with VPA. The results show that VPA promote cell death by altering metabolic pathways principally pentose phosphate pathway (PPP) and 2 ' deoxy-alpha-D-ribose-1-phosphate degradation related with metabolites that decrease cell proliferation and cell growth, interfere with energy sources and enhance reactive oxygen species (ROS) levels. We even suggest that mechanisms such as ferropoptosis could be involved due to deregulation of L-cysteine. These results suggest that VPA has different pharmacological mechanisms in killing cancer cells including apoptotic and nonapoptotic mechanisms, and due to the broad impact that HDACis have in cells, metabolomic approaches are a great source of information to generate new insights for this type of molecule.
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