阿霉素

蒽环霉素抗生素;抑制DNA拓扑异构酶II

产品号 #(选择产品)

产品号 #100-0558_C

蒽环霉素抗生素;抑制DNA拓扑异构酶II

概述

阿霉素是一种蒽环类抗生素,可插入DNA并抑制DNA拓扑异构酶II (Burridge等人;Lorenzo等人)。阿霉素表现出心脏毒性作用,包括产生活性氧、抑制DNA拓扑异构酶II和释放肌浆网中的钙(Burridge等)。本品以分子的盐酸盐形式供应。

癌症研究
·诱导人内皮细胞凋亡(Lorenzo等人)。

Alternative Names
DOX
 
Cell Type
Cancer Cells and Cell Lines, Endothelial Cells
 
Area of Interest
Cancer, Endothelial Cell Biology
 
CAS Number
25316-40-9
 
Chemical Formula
C27H29NO11 • HCl
 
Molecular Weight
580 g/mol
 
Purity
≥ 98%
 
Pathway
p53
 

Protocols and Documentation

Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.

Document Type
Product Name
Catalog #
Lot #
Language
Catalog #
100-0559, 100-0558
Lot #
All
Language
English
Document Type
Safety Data Sheet
Catalog #
100-0559, 100-0558
Lot #
All
Language
English

Resources and Publications

Educational Materials (2)

Publications (2)

Human induced pluripotent stem cell-derived cardiomyocytes recapitulate the predilection of breast cancer patients to doxorubicin-induced cardiotoxicity. P. W. Burridge et al. Nature medicine 2016

Abstract

Doxorubicin is an anthracycline chemotherapy agent effective in treating a wide range of malignancies, but it causes a dose-related cardiotoxicity that can lead to heart failure in a subset of patients. At present, it is not possible to predict which patients will be affected by doxorubicin-induced cardiotoxicity (DIC). Here we demonstrate that patient-specific human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) can recapitulate the predilection to DIC of individual patients at the cellular level. hiPSC-CMs derived from individuals with breast cancer who experienced DIC were consistently more sensitive to doxorubicin toxicity than hiPSC-CMs from patients who did not experience DIC, with decreased cell viability, impaired mitochondrial and metabolic function, impaired calcium handling, decreased antioxidant pathway activity, and increased reactive oxygen species production. Taken together, our data indicate that hiPSC-CMs are a suitable platform to identify and characterize the genetic basis and molecular mechanisms of DIC.
Doxorubicin induces apoptosis and CD95 gene expression in human primary endothelial cells through a p53-dependent mechanism. E. Lorenzo et al. The Journal of biological chemistry 2002 mar

Abstract

Regulation of the homeostasis of vascular endothelium is critical for the processes of vascular remodeling and angiogenesis under physiological and pathological conditions. Here we show that doxorubicin (Dox), a drug used in antitumor therapy, triggered a marked accumulation of p53 and induced CD95 gene expression and apoptosis in proliferating human umbilical vein endothelial cells (HUVECs). Transfection and site-directed mutagenesis experiments using the CD95 promoter fused to an intronic enhancer indicated the requirement for a p53 site for Dox-induced promoter activation. Furthermore, the p53 inhibitor pifithrin-alpha (PFT-alpha) blocked both promoter inducibility and protein up-regulation of CD95 in response to Dox. Up-regulated CD95 in Dox-treated cells was functional in eliciting apoptosis upon incubation of the cells with an agonistic CD95 antibody. However, Dox-mediated apoptosis was independent of CD95/CD95L interaction. The analysis of apoptosis in the presence of PFT-alpha and benzyloxycarbonyl-Val-Ala-dl-Asp-fluoromethylketone revealed that both p53 and caspase activation are required for Dox-mediated apoptosis of HUVECs. Finally, Dox triggered Bcl-2 down-regulation, cytochrome c release from mitochondria, and the activation of caspases 9 and 3, suggesting the involvement of a mitochondrially operated pathway of apoptosis. These results highlight the role of p53 in the response of primary endothelial cells to genotoxic drugs and may reveal a novel mechanism underlying the antitumoral properties of Dox, related to its ability to induce apoptosis in proliferating endothelial cells.

更多信息

更多信息
Molecular Weight 580 g/mol
Alternative Names DOX
Cas Number 25316-40-9
Chemical Formula C27H29NO11 • HCl
Purity ≥ 98%
Pathway p53
PRODUCTS ARE FOR RESEARCH USE ONLY AND NOT INTENDED FOR HUMAN OR ANIMAL DIAGNOSTIC OR THERAPEUTIC USES UNLESS OTHERWISE STATED. FOR ADDITIONAL INFORMATION ON QUALITY AT STEMCELL, REFER TO WWW.STEMCELL.COM/COMPLIANCE. Safety Statement: CA WARNING: This product can expose you to Doxorubicin hydrochloride (Adriamycin) which is known to the State of California to cause cancer and birth defects or other reproductive harm. For more information go to www.P65Warnings.ca.gov
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