Targeted Cancer Therapy with a 2-Deoxyglucose―Based Adriamycin Complex

Adriamycin (ADM) has been effective against many types of solid tumors in clinical applications. However, its use is limited because of systemic toxicities, primarily cardiotoxicity, and multidrug resistance. In this study, a new active receptor-mediated complex, ADM conjugated with 2-amino-2-deoxy-...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2013-02, Vol.73 (4), p.1362-1373
Main Authors: JIE CAO, SISI CUI, SIWEN LI, CHANGLI DU, JUNMEI TIAN, SHUNAN WAN, ZHIYU QIAN, YUEQING GU, CHEN, Wei R, GUANGJI WANG
Format: Article
Language:English
Subjects:
Animals
Antibiotics, Antineoplastic - chemistry
Antibiotics, Antineoplastic - pharmacology
Antineoplastic agents
Biological and medical sciences
Cell Line, Tumor
Cell Survival - drug effects
Chemistry, Pharmaceutical - methods
Deoxyglucose - chemistry
Doxorubicin - chemistry
Doxorubicin - pharmacology
Glucose Transporter Type 1 - antagonists & inhibitors
Glucose Transporter Type 1 - genetics
Glucose Transporter Type 1 - metabolism
Hep G2 Cells
Humans
MCF-7 Cells
Medical sciences
Mice
Mice, Nude
Microscopy, Confocal
Models, Chemical
Molecular Structure
Neoplasms - drug therapy
Neoplasms - genetics
Neoplasms - pathology
Pharmacology. Drug treatments
Quercetin - pharmacology
Succinic Acid - chemistry
Tumor Burden - drug effects
Tumors
Xenograft Model Antitumor Assays
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Summary:Adriamycin (ADM) has been effective against many types of solid tumors in clinical applications. However, its use is limited because of systemic toxicities, primarily cardiotoxicity, and multidrug resistance. In this study, a new active receptor-mediated complex, ADM conjugated with 2-amino-2-deoxy-d-glucose and succinic acid (2DG-SUC-ADM), was designed to target tumor cells through glucose transporter 1 (GLUT1). MTT assay and confocal images showed that the complex had better inhibition rate to tumor cells and low toxicity to normal cells. Most importantly, the complex displayed a potential to reverse overcome multidrug resistance in cancer cells, with more complex transported into the nucleus of tumor cells. Our in vivo experiments also showed that this new complex could significantly decrease organ toxicity and enhance the antitumor efficacy compared with free ADM, indicating a promising drug of 2DG-SUC-ADM for targeted cancer therapy.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-12-2072