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Anticonvulsant valproic acid and other short-chain fatty acids as novel anticancer therapeutics: Possibilities and
Katarzyna Lipska1, Anna Gumieniczek1, Agata A Filip2
1Chair and Department of Medicinal Chemistry,Medical University of Lublin20-090Lublin, Poland.
Abstract:
Results from numerous pre-clinical studies suggest that a well known anticonvulsant drug valproic acid (VPA) and other short-chain fatty acids (SCFAs) cause significant inhibition of cancer cell proliferation by modulating multiple signaling pathways. First of all, they act as histone deacetylase (HDAC) inhibitors (HDIs), being involved in the epigenetic regulation of gene expression. Afterward, VPA is shown to induce apoptosis and cell differentiation, as well as regulate Notch signaling. Moreover, it up-regulates the expression of certain G protein-coupled receptors (GPCRs), which are involved in various signaling pathways associated with cancer. As a consequence, some pre-clinical and clinical trials were carried out to estimate anticancer effectiveness of VPA, in monotherapy and in new drug combinations, while other SCFAs were tested in pre-clinical studies. The present manuscript summarizes the most important information from the literature about their potent anticancer activities to show some future perspectives related to epigenetic therapy.
Insights
Valproic acid (VPA) and short-chain fatty acids (SCFAs) show anticancer potential by inhibiting cancer cell growth through epigenetic mechanisms like HDAC inhibition. Further research explores their use in epigenetic therapy for cancer treatment.
Area of Science:
- Oncology
- Epigenetics
- Pharmacology
Background:
- Anticonvulsant valproic acid (VPA) and other short-chain fatty acids (SCFAs) exhibit anticancer properties.
- These compounds modulate critical cancer signaling pathways.
Purpose of the Study:
- To review the literature on the anticancer activities of VPA and SCFAs.
- To highlight their potential in epigenetic therapy.
Main Methods:
- Review of pre-clinical and clinical studies on VPA and SCFAs.
- Analysis of their mechanisms of action, including HDAC inhibition, apoptosis induction, and GPCR regulation.
Main Results:
- VPA and SCFAs inhibit cancer cell proliferation via multiple signaling pathways.
- They act as histone deacetylase inhibitors (HDACIs), influencing gene expression epigenetically.
- VPA also induces apoptosis, cell differentiation, regulates Notch signaling, and up-regulates G protein-coupled receptors (GPCRs).
Conclusions:
- VPA and SCFAs demonstrate significant anticancer potential.
- Their epigenetic mechanisms offer promising avenues for novel cancer therapies.
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