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.
journal_name
Curr Cancer Drug Targetsjournal_title
Current cancer drug targetsauthors
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 Pdoi
10.2174/156800909789057024subject
Has Abstractpub_date
2009-08-01 00:00:00pages
675-89issue
5eissn
1568-0096issn
1873-5576pii
CCDT-ABS-07journal_volume
9pub_type
杂志文章abstract::Membrane ion channels participate in cancerous processes such as proliferation, migration and invasion, which contribute to metastasis. Increasing evidence indicates that voltage-dependent K(+) (Kv) channels are involved in the proliferation of many types of cells, including tumor cells. Kv channels have generated imm...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800909790192400
更新日期:2009-12-01 00:00:00
abstract::Exosomes are small vesicles that are secreted by various types of cells, known to mediate signal transduction between cells. During recent years, novel carriers for the delivery of targeted drugs, chemotherapy drugs and RNAs are under development, which is believed to be beneficial for patients. Considering issues of ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009617666170710120311
更新日期:2018-01-01 00:00:00
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journal_title:Current cancer drug targets
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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journal_title:Current cancer drug targets
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journal_title:Current cancer drug targets
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journal_title:Current cancer drug targets
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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journal_title:Current cancer drug targets
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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更新日期:2011-02-01 00:00:00
abstract::The histone deacetylase inhibitors are a new class of cytostatic agents that inhibit the proliferation of tumor cells in culture and in vivo by inducing cell cycle arrest, differentiation and/or apoptosis. Histone acetylation and deacetylation play important roles in the modulation of chromatin topology and the regula...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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更新日期:2004-03-01 00:00:00
abstract::Actin was first identified in non-muscle cells only about three decades ago, and at about the same time, it was found that actin filaments were disrupted in the malignant transformed cells. The actin network is a rather complex, yet important structural and functional system of all eukaryotic cells. Actin filaments pr...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009043332998
更新日期:2004-06-01 00:00:00
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009619666190802135714
更新日期:2019-01-01 00:00:00
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journal_title:Current cancer drug targets
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更新日期:2001-05-01 00:00:00
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009615666150211104524
更新日期:2015-01-01 00:00:00
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800907781386579
更新日期:2007-08-01 00:00:00
abstract:BACKGROUND:Approximately one third of Diffuse Large B cell Lymphomas (DLBCL) are refractory or relapse. Novel therapeutic approaches under scrutiny include inhibitors of B-cell receptor (BCR) signaling. Protein kinase CK2 propels survival, proliferation and stress response in solid and hematologic malignancies and prom...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009617666170427110450
更新日期:2018-01-01 00:00:00
abstract::The total expression profiles of two medulloblastoma cell lines resistant to the preactivated form of cyclophosphamide (4-hydroperoxycyclophosphamide, 4-HC) were examined using the Affymetrix GeneChip U133A array. Our primary objective was to look for possible genes, other than the well-studied aldehyde dehydrogenases...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800908784293631
更新日期:2008-05-01 00:00:00
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journal_title:Current cancer drug targets
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doi:10.2174/156800910791517172
更新日期:2010-08-01 00:00:00
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pub_type: 杂志文章,评审
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009616666160813191809
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更新日期:2008-11-01 00:00:00
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journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009620666201116112937
更新日期:2020-11-15 00:00:00
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journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800911794519761
更新日期:2011-03-01 00:00:00
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009043332925
更新日期:2004-08-01 00:00:00
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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更新日期:2007-05-01 00:00:00
abstract::The evolution of genomic research enabled the genetic and molecular profiling of breast cancer and revealed the profound complexity and heterogeneity of this disease. Subtypes of breast cancer characterized by mutations and/or amplifications of some proto-oncogenes are associated with an increased rate of recurrence a...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Epidermal growth factor receptor (EGFR) is a well-recognised drug target exploited for treating non-small cell lung cancer (NSCLC). Gefitinib and erlotinib are first generation clinically employed inhibitors used against EGFR activating mutants. However, during course of treatment these inhibitors become ine...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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更新日期:2017-01-01 00:00:00
abstract::Heat shock proteins (HSPs) are molecular chaperones that stabilize folding and conformation of normal as well as oncogenic proteins. These chaperones thereby prevent the formation of protein aggregates. HSPs are often overexpressed in human malignancies, including AML. HSP90 is the main chaperon required for the stabi...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800909789271486
更新日期:2009-09-01 00:00:00
abstract::Polysialic acid (polySia) is a carbohydrate polymer critical for neuronal cell migration and axon pathfinding in embryonic development. Besides brain regions requiring persistent neuronal plasticity, polySia is essentially absent from the adult body. However, polySia is aberrantly re-expressed on many tumours, where i...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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更新日期:2012-10-01 00:00:00