AI Article Synopsis
- Ovarian cancer treatment is challenging due to limited selective drugs and resistance to platinum-based therapies, prompting interest in combination therapy with epigenetic drugs.
- Two HDAC inhibitors (sodium butyrate and SAHA) combined with calpeptin were tested on ovarian cancer cell lines CAOV-3 and SKOV-3, showing enhanced growth inhibition and re-expression of tumor suppressor genes.
- The findings suggest that re-expressing these genes can sensitize ovarian cancer cells to treatments, leading to apoptosis and autophagy as mechanisms of cell death.
Article Abstract
Background: Ovarian cancer is difficult to treat due to absence of selective drugs and tendency of platinum drugs to promote resistance. Combination therapy using epigenetic drugs is predicted to be a beneficial alternative.
Materials And Methods: This study investigated the effects of combination therapies using two structurally different histone deacetylase (HDAC) inhibitors (HDACi), sodium butyrate and suberanilohydroxamic acid (SAHA), with the calpain inhibitor calpeptin on two characteristically different ovarian cancer cell lines, CAOV-3 and SKOV-3.
Results: Suboptimal doses of HDACi and calpeptin produced several effects. Growth inhibition was enhanced and the epigenetically silenced tumor suppressor genes ARHI, p21 and RARβ2 were re-expressed. Methylation of specific CpG residues in ARHI were reduced. Cell-cycle progression was inhibited and apoptosis, as well as autophagy, were induced. The phosphorylation of ERK and Akt were differentially effected by these inhibitors.
Conclusion: The re-expression of tumor suppressors may sensitize ovarian cancer cells, which then undergo apoptosis and autophagy for cell death.
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| http://dx.doi.org/10.21873/anticanres.11156 | DOI Listing |
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