https://nova.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22877 Wed 11 Apr 2018 13:19:11 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:26547 in vitro and in vivo. PI staining showed significant apoptosis in NPC cells accompanied by the overproduction of ROS and downregulation of mitochondrial membrane potential (MMP, ΔΨm) by 3-BrPA. However, the ROS scavenger N-acetyl-L-cysteine (NAC) significantly reduced 3-BrPA-induced apoptosis by decreasing ROS and facilitating the recovery of MMP. We elucidated the molecular mechanisms underlying 3-BrPA activity and found that it caused mitochondrial dysfunction and ROS production, leading to necroptosis of NPC cells. We investigated the effects of the caspase inhibitor z-VAD-fmk, which inhibits apoptosis but promotes death domain receptor (DR)-induced NPC cell necrosis. Necrostatin-1 (Nec-1) inhibits necroptosis, apparently via a DR signaling pathway and thus abrogates the effects of z-VAD‑fmk. In addition, we demonstrated the effective attenuation of 3-BrPA-induced necrotic cell death by Nec-1. Finally, animal studies proved that 3-BrPA exhibited significant antitumor activity in nude mice. The present study is the first demonstration of 3-BrPA-induced non-apoptotic necroptosis and ROS generation in NPC cells and provides potential strategies for developing agents against apoptosis‑resistant cancers.]]> Wed 11 Apr 2018 11:05:32 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49002 Wed 03 May 2023 12:09:58 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51639 Tue 12 Sep 2023 20:15:00 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:25166 Thu 03 Feb 2022 12:22:19 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:18006 Sat 24 Mar 2018 07:56:16 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22689 Streptomyces hygroscopicus. In the present study, we examined the anticancer effects of 17-DR on human hepatocellular carcinoma (HCC) cell lines HepG2 and SMMC7721, and its underlying mechanisms. The results indicated that 17-DR could concentration-dependently inhibit the proliferation, and decrease the colony formation in HCC cells. It also induced significant apoptosis in HCC cells, which was mediated by mitochondria via a caspase-dependent pathway. The mechanisms involved in 17-DR-induced apoptosis included the downregulation of myeloid cell leukemia-1 (Mcl-1), and upregulation of Bcl-2 antagonist killer 1 (Bak). And the upregulated Bak expression resulted from downregulation of Mcl-1 played an essential role in this process. Taken together, these results indicated that 17-DR possessed potent anticancer effects on HCC cells by inhibiting cell proliferation and inducing apoptosis.]]> Sat 24 Mar 2018 07:11:11 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:52684 Fri 20 Oct 2023 09:58:07 AEDT ]]>