Histone Deacetylase Inhibitor-Induced Autophagy in Tumor Cells: Implications for p53
AbstractAutophagy is an essential process of the eukaryotic cell allowing degradation and recycling of dysfunctional cellular components in response to either physiological or pathological changes. Inhibition of autophagy in combination with chemotherapeutic treatment has emerged as a novel approach in cancer treatment leading to cell cycle arrest, differentiation, and apoptosis. Suberoyl hydroxamic acid (SAHA) is a broad-spectrum histone deacetylase inhibitor (HDACi) suppressing family members in multiple HDAC classes. Increasing evidence indicates that SAHA and other HDACi can, in addition to mitochondria-mediated apoptosis, also promote caspase-independent autophagy. SAHA-induced mTOR inactivation as a major regulator of autophagy activating the remaining autophagic core machinery is by far the most reported pathway in several tumor models. However, the question of which upstream mechanisms regulate SAHA-induced mTOR inactivation that consequently initiate autophagy has been mainly left unexplored. To elucidate this issue, we recently initiated a study clarifying different modes of SAHA-induced cell death in two human uterine sarcoma cell lines which led to the conclusion that the tumor suppressor protein p53 could act as a molecular switch between SAHA-triggered autophagic or apoptotic cell death. In this review, we present current research evidence about HDACi-mediated apoptotic and autophagic pathways, in particular with regard to p53 and its therapeutic implications. View Full-Text
Scifeed alert for new publicationsNever miss any articles matching your research from any publisher
- Get alerts for new papers matching your research
- Find out the new papers from selected authors
- Updated daily for 49'000+ journals and 6000+ publishers
- Define your Scifeed now
Mrakovcic, M.; Kleinheinz, J.; Fröhlich, L.F. Histone Deacetylase Inhibitor-Induced Autophagy in Tumor Cells: Implications for p53. Int. J. Mol. Sci. 2017, 18, 1883.
Mrakovcic M, Kleinheinz J, Fröhlich LF. Histone Deacetylase Inhibitor-Induced Autophagy in Tumor Cells: Implications for p53. International Journal of Molecular Sciences. 2017; 18(9):1883.Chicago/Turabian Style
Mrakovcic, Maria; Kleinheinz, Johannes; Fröhlich, Leopold F. 2017. "Histone Deacetylase Inhibitor-Induced Autophagy in Tumor Cells: Implications for p53." Int. J. Mol. Sci. 18, no. 9: 1883.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.