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SHR Neuro Krebs Kardio Lipid

Gleixner, KV; Mayerhofer, M; Vales, A; Gruze, A; Hörmann, G; Cerny-Reiterer, S; Lackner, E; Hadzijusufovic, E; Herrmann, H; Iyer, AK; Krauth, MT; Pickl, WF; Marian, B; Panzer-Grümayer, R; Sillaber, C; Maeda, H; Zielinski, C; Valent, P.
Targeting of hsp32 in solid tumors and leukemias: a novel approach to optimize anticancer therapy.
Curr Cancer Drug Targets. 2009; 9(5): 675-689.
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Autor/innen der Med Uni Graz:
Lackner Eva-Maria
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Abstract:
Heat shock protein 32 (Hsp32), also known as heme oxygenase-1 (HO-1), is a stress-related anti-apoptotic molecule, that has been implicated in enhanced survival of neoplastic cells and in drug-resistance. We here show that Hsp32 is expressed in most solid tumors and hematopoietic neoplasms and may be employed as a new therapeutic target as evidenced by experiments using specific siRNA and a Hsp32-targeting pharmacologic inhibitor. This Hsp-32 targeting drug, SMA-ZnPP, was found to inhibit the proliferation of neoplastic cells with IC(50) values ranging between 1 and 50 microM. In addition, SMA-ZnPP induced apoptosis in all neoplastic cells examined. Furthermore, SMA-ZnPP was found to synergize with other targeted and conventional drugs in producing growth-inhibition. Resulting synergistic effects were observed in all tumor and leukemia cells examined. Interestingly, several of the drug partners, when applied as single agents, induced the expression of Hsp32 in neoplastic cells, suggesting that synergistic effects resulted from SMA-ZnPP-induced ablation of a Hsp32-mediated survival-pathway that is otherwise used by tumor cells to escape drug-induced apoptosis. Together, Hsp32 is an important survival factor and target in solid tumors and hematopoietic neoplasms, and may be used to optimize anticancer therapy by combining conventional or targeted drugs with Hsp32-inhibitors. Based on these data, it seems desirable to explore the value of Hsp32-targeting drugs as anti-cancer agents in clinical trials.
Find related publications in this database (using NLM MeSH Indexing)
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
Cell Line, Tumor -
Cell Survival - drug effects
Drug Delivery Systems -
Drug Screening Assays, Antitumor -
Drug Synergism -
Enzyme Induction - drug effects
Female -
Heme Oxygenase-1 - antagonists and inhibitors
Humans -
Leukemia - drug therapy
Maleates - pharmacology
Metalloporphyrins - pharmacology
Neoplasms - drug therapy
Neoplastic Stem Cells - drug effects
Oncogene Proteins - metabolism
Polystyrenes - pharmacology
RNA, Messenger - metabolism
RNA, Small Interfering - pharmacology

Find related publications in this database (Keywords)
Solid tumors
Leukemias
HO-1
Hsp32
SMA-ZnPP
targeted drugs
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