Trichostatin A inhibits proliferation of triple negative breast cancer cells by inducing cell cycle arrest and apoptosis

Abstract

Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with poor outcome. Because of lacking therapeutic targets, chemotherapy is the main treatment option for patients with TNBC. Overexpression of HDACs correlates with tumorigenesis, highlighting the potential of HDACs as therapeutic targets for TNBC. Here we demonstrate that trichostatin A (TSA, a HDAC inhibitor) selectively inhibits the proliferation of TNBC cell lines HCC1806 and HCC38 rather than a normal breast cell line MCF10A. The inhibition of TNBC by TSA is via its roles in inducing cell cycle arrest and apoptosis. TSA treatment leads to decreased expression of CYCLIN D1, CDK4, CDK6 and BCL-XL, but increased P21 expression. Moreover, combination of TSA with doxorubicin has synergistic effects on inhibiting proliferation of HCC1806 and HCC38 cells. Our studies identified a promising epigenetic-based therapeutic strategy that may be implemented in the therapy of fatal human breast cancer.

CHFR regulates chemoresistance in triple-negative breast cancer through destabilizing ZEB1

“…Since ZEB1 is a transcriptional factor that is not easily druggable, indirectly inactivating ZEB1 by TSA open a new window for resistant TNBC. Notably, instead of directly affecting cyclinD1, CDK4/6, and BCL-XL [ 43 ], we found that co-treatment with TSA and chemotherapeutic drugs could synergistically inhibit cell viability by inducing apoptosis, which is clearly mediated by CHFR. In patients with breast cancer, CHFR was found to positively correlate with poor survival (both mesenchymal and basal-like 1 malignant breast cancer).…”

MicroRNA‑615‑5p regulates the proliferation and apoptosis of breast cancer cells by targeting HSF1

“…Furthermore, cyclin D1 was found to be overexpressed in breast cancer tissues, suggesting that it may serve as a potential biomarker (31). A number of studies have indicated that the suppression of cyclin D1 may inhibit breast cancer cell proliferation (32)(33)(34). Furthermore, the forced expression of HSF1 has been shown to increase the expression of cyclin D1 (35).…”

Investigational Drug Treatments for Triple-Negative Breast Cancer

“…The same year, Song et al reported a study in which the inhibition of TNBC by trichostatin A (TSA), an HDACI, was investigated [ 67 ]. The experimental findings indicated that TSA treatment results in decreased expression of CYCLIN D1, CDK4, CDK6, and BCL-XL, but increased P21 expression.…”

“…SAHA managed to inhibit effectively the growth of TNBC cells. The combinations of OBP-801 with eribulin and TSA with doxorubicin led to promising therapeutic strategies, through synergistic action with other agents such as olaparib, entinostat, and eribulin [ 65 , 66 , 67 , 68 , 69 ]. They induce apoptosis and inhibit angiogenesis.…”