Panobinostat mediated cell death: a novel therapeutic approach for osteosarcoma.

Panobinostat mediated cell death: a novel therapeutic approach for osteosarcoma. Oncotarget. 2018 Aug 31;9(68):32997-33010 Authors: Wirries A, Jabari S, Jansen EP, Roth S, Figueroa-Juárez E, Wissniowski TT, Neureiter D, Klieser E, Lechler P, Ruchholtz S, Bartsch DK, Boese CK, Di Fazio P Abstract Osteosarcoma is an aggressive cancer with a poor long term prognosis. Neo-adjuvant poly-chemotherapy followed by surgical resection remains the standard treatment, which is restricted by multi-drug resistance. If first-line therapy fails, disease control and patient survival rate drop dramatically. We aimed to identify alternative apoptotic mechanisms induced by the histone deacetylase inhibitor panobinostat in osteosarcoma cells. Saos-2, MG63 and U2-OS osteosarcoma cell lines, the immortalized human osteoblast line hFOB and the mouse embryo osteoblasts (MC3T3-E1) were treated with panobinostat. Real time viability and FACS confirmed the cytotoxicity of panobinostat. Cell stress/death related factors were analysed by RT-qPCR and western blot. Cell morphology was assessed by electron microscopy. 10 nM panobinostat caused cell viability arrest and death in all osteosarcoma and osteoblast cells. P21 up-regulation was observed in osteosarcoma cells, while over-expression of p73 was restricted to Saos-2 (TP53-/-). Survivin and Bcl-2 were suppressed by panobinostat. Endoplasmic reticulum (ER) stress markers BiP, CHOP, ATF4 and ATF6 were induced in...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research