https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29220 Wed 19 Jan 2022 15:15:55 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14354 V600E melanoma cells by induction of necrosis. Cotreatment with the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) or panobinostat (LBH589) and the BRAF inhibitor PLX4720 activated the caspase cascade, but caspases appeared dispensable for killing, in that inhibition of caspases did not invariably block induction of cell death. The majority of dying cells acquired propidium iodide positivity instantly when they became positive for Annexin V, suggesting induction of necrosis. This was supported by caspase-independent release of high-mobility group protein B1, and further consolidated by rupture of the plasma membrane and loss of nuclear and cytoplasmic contents, as manifested by transmission electron microscopic analysis. Of note, neither the necrosis inhibitor necrostatin-1 nor the small interference RNA (siRNA) knockdown of receptor-interacting protein kinase 3 (RIPK3) inhibited cell death, suggesting that RIPK1 and RIPK3 do not contribute to induction of necrosis by combinations of HDAC and BRAF inhibitors in BRAF^V600E melanoma cells. Significantly, SAHA and the clinically available BRAF inhibitor vemurafenib cooperatively inhibited BRAF^V600E melanoma xenograft growth in a mouse model even when caspase-3 was inhibited. Taken together, these results indicate that cotreatment with HDAC and BRAF inhibitors can bypass canonical cell death pathways to kill melanoma cells, which may be of therapeutic advantage in the treatment of melanoma.]]> Wed 11 Apr 2018 17:05:48 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17258 Wed 11 Apr 2018 11:05:43 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17266 Wed 11 Apr 2018 10:51:24 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30753 Thu 03 Feb 2022 12:21:59 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17503 Sat 24 Mar 2018 08:04:05 AEDT ]]>