https://novaprd-lb.newcastle.edu.au/vital/access/manager/Index ${session.getAttribute("locale")} 5 INPP4B is an oncogenic regulator in human colon cancer https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:29220 Wed 19 Jan 2022 15:15:55 AEDT ]]> Cotargeting histone deacetylases and oncogenic BRAF synergistically kills human melanoma cells by necrosis independently of RIPK1 and RIPK3 https://novaprd-lb.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 BRAFV600E melanoma cells. Significantly, SAHA and the clinically available BRAF inhibitor vemurafenib cooperatively inhibited BRAFV600E 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 ]]> Apoptosis of human melanoma cells induced by inhibition of B-RAFᵛ⁶⁰⁰ᴱ involves preferential splicing of bimS https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:9452 Wed 11 Apr 2018 14:22:54 AEST ]]> Targeting anti-apoptotic mechanisms for reversal of resistance to BRAF inhibitors in melanoma https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:13255 Sat 24 Mar 2018 08:16:00 AEDT ]]> Adipocytes contribute to resistance of human melanoma cells to chemotherapy and targeted therapy https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:21445 Sat 24 Mar 2018 08:05:44 AEDT ]]>