human
The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
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    INPUT: Zinc dyshomeostasis can induce cell death . However , the mechanisms involved have not been fully elucidated in prostate cancer ( PCa ) cells , which differ dramatically from normal cells in their zinc handling ability . Here , we studied the effects of the ionophore Zn-pyrithione ( ZP ) and the chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine ( TPEN ) . Both compounds induced cell death at micromolar concentrations when incubated with androgen-dependent ( LNCaP ) , androgen-independent ( PC3 , DU145 ) and androgen-sensitive ( C4-2 ) PCa cell-lines . Compared to PCa cells , RWPE1 prostate epithelial cells were less sensitive to ZP and more sensitive to TPEN , but total cellular zinc levels were changed similarly . ZnSO4 enhanced the toxicity of ZP , but inhibited the effects of TPEN as expected . The morphological/biochemical responses to ZP and TPEN differed . ZP decreased ATP levels and stimulated ERK , AKT and PKC phosphorylation . DNA laddering was observed only at low doses of ZP but all doses of TPEN . TPEN activated caspase 3/7 and induced PARP-cleavage , DNA-fragmentation , ROS-formation and apoptotic bodies . PKC and ERK-pathway inhibitors , and antioxidants protected against ZP-induced but not TPEN-induced death . Inhibitors of MPTP-opening protected both . Cell death in response to TPEN ( but not ZP ) was diminished by a calpain inhibitor and largely prevented by a caspase 3 inhibitor . Overall , the results indicated primarily a necrotic cell death for ZP and an apoptotic cell death for TPEN . The enhanced sensitivity of PCa cells to ZP and the apparent ability of ZP and TPEN to kill quiescent and rapidly dividing cells in a p53-independent manner suggest that ZP/TPEN might be used to develop adjunct treatments for PCa .
    OUTPUT:

agent
resisting cell death
The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
    ###
    INPUT: Zinc dyshomeostasis can induce cell death . However , the mechanisms involved have not been fully elucidated in prostate cancer ( PCa ) cells , which differ dramatically from normal cells in their zinc handling ability . Here , we studied the effects of the ionophore Zn-pyrithione ( ZP ) and the chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine ( TPEN ) . Both compounds induced cell death at micromolar concentrations when incubated with androgen-dependent ( LNCaP ) , androgen-independent ( PC3 , DU145 ) and androgen-sensitive ( C4-2 ) PCa cell-lines . Compared to PCa cells , RWPE1 prostate epithelial cells were less sensitive to ZP and more sensitive to TPEN , but total cellular zinc levels were changed similarly . ZnSO4 enhanced the toxicity of ZP , but inhibited the effects of TPEN as expected . The morphological/biochemical responses to ZP and TPEN differed . ZP decreased ATP levels and stimulated ERK , AKT and PKC phosphorylation . DNA laddering was observed only at low doses of ZP but all doses of TPEN . TPEN activated caspase 3/7 and induced PARP-cleavage , DNA-fragmentation , ROS-formation and apoptotic bodies . PKC and ERK-pathway inhibitors , and antioxidants protected against ZP-induced but not TPEN-induced death . Inhibitors of MPTP-opening protected both . Cell death in response to TPEN ( but not ZP ) was diminished by a calpain inhibitor and largely prevented by a caspase 3 inhibitor . Overall , the results indicated primarily a necrotic cell death for ZP and an apoptotic cell death for TPEN . The enhanced sensitivity of PCa cells to ZP and the apparent ability of ZP and TPEN to kill quiescent and rapidly dividing cells in a p53-independent manner suggest that ZP/TPEN might be used to develop adjunct treatments for PCa .
    OUTPUT:
