Exploring the potential of Gonolobus condurango as a histone deacetylase inhibitor in triple-negative breast cancer cell lines: in vitro study.

Abstract

Background: Triple-negative breast cancer (TNBC) is a subtype associated with poor prognosis, low survival rates, and high expression of histone deacetylases (HDAC). Treatment with HDAC inhibitors (HDACi) induces the acetylation of histones and thereby the expression of tumor suppressive miRNAs that regulate proliferation, apoptosis, migration, and differentiation. Gonolobus condurango (GC) has been reported to exhibit HDAC inhibitory effects, and this study aims to investigate whether GC acts as a HDACi in TNBC cell lines.

Methods: Expression and acetylation analyses were performed on the TNBC cell lines HCC38, HCC1395, and HCC1937. Cells were treated with HDAC inhibitors Trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA), or Romidepsin as well as with GC Urtincture and different dilutions of GC. Tumor-relevant functional effects were analyzed using WST-1-based proliferation and Caspase-3/7 based apoptosis assays. Induction of expression of tumor-suppressive miRNAs hsa-miRNA-192-5p (miR-192) and hsa-miR-194-2 (miR-194) was analyzed by qRT-PCR.

Results: Meta-analyses of gene expression showed a significant reduction in HDAC1 and HDAC2 expression in triple-negative breast cancer samples. The TNBC cell lines (HCC38, HCC1395, and HCC1937) used for in vitro assays also exhibited reduced expression of HDAC1, HDAC2, HDAC3, and HDAC4 and low acetylation levels. Treatment with the HDAC inhibitors TSA, SAHA, or Romidepsin induced acetylation, while GC did not. TSA and GC Urtincture induced apoptosis in HCC38, whereas GC dilutions had no effect. Treatment with TSA forced the expression of tumor suppressive miRNAs miR-192 and miR-194, but neither GC Urtincture nor any GC dilution induced the expression of these miRNAs.

Conclusion: Several classes of HDAC inhibitors have been shown to be potent and specific anticancer agents. In this study, Gonolobus condurango showed no HDAC inhibitory effect in the TNBC cell lines. Identifying new HDAC inhibitors is important, but they must be well characterized before being used as therapeutic agents in humans.