Histone deacetylase inhibitors specifically kill nonproliferating tumour cells

WZ4002, a third-generation EGFR inhibitor, can overcome anoikis resistance in EGFR-mutant lung adenocarcinomas more efficiently than Src inhibitors

“…HDAC inhibitors have proapoptotic effects on quiescent cancer stem cells or slowly cycling cells that often resist therapy and serve as the source of relapse by reducing Wnt signaling, which has a critical role in stem cell maintenance, or by inhibiting the chaperone function of heat shock protein 90. 13,31,32 Our results suggest that H1975 SR cells have slowly growing subpopulations that are sensitive to HDAC inhibitors. However, the molecular mechanisms underlying the proapoptotic effect of TSA on these subpopulations in H1975 SR cells remain to be elucidated.…”

Histone deacetylase inhibitors: molecular mechanisms of action

“…Normal cells are relatively resistant to HDACi-induced cell death (Burgess et al, 2004;Insinga et al, 2005;Ungerstedt et al, 2005). The cell death pathways identified in mediating HDACiinduced transformed cell death include apoptosis (Rosato and Grant, 2005;Bolden et al, 2006;Minucci and Pelicci, 2006) by the intrinsic (Ruefli et al, 2001) and extrinsic pathways, mitotic catastrophe/cell death (Qiu et al, 2000;Dowling et al, 2005;Xu et al, 2005), autophagic cell death (Shao et al, 2004), senescence and reactive oxygen species (ROS)-facilitated cell death (Rosato and Grant, 2005;Ungerstedt et al, 2005).…”

“…Transformed cells sensitive to HDACi-induced cell death are generally cell growth-arrested with increase of p21 expression (Huang and Pardee, 2000;Xu et al, 2006). HDACi can kill both proliferating and non-proliferating cells (Burgess et al, 2004). This is in contrast to the action of many chemotherapeutic drugs, which are effective only on proliferating cells.…”

Histone Deacetylase Inhibitors for Cancer Therapy

“…[1][2][3][4][5][6][7][8] In addition, HDACIs have the advantage of being less toxic in normal cells than in cancer cells. [10][11][12][13][14] Based on their pleiotropic cellular effects and their tumor-selectivity, several HDACIs are currently undergoing clinical trials, and some of them have shown promising anti-tumor activity. [15][16][17][18][19][20][21] While it is clear that HDACIs directly modulate gene transcription by histone hyperacetylation, the molecular underpinnings of their cytotoxicity and tumor-selectivity remain poorly understood.…”