Journal
JOURNAL OF CONTROLLED RELEASE
Volume 124, Issue 1-2, Pages 6-10Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2007.08.016
Keywords
HPMA copolymer; doxorubicin; cell cycle; ovarian cancer
Funding
- NCI NIH HHS [R01 CA051578, CA51578, R01 CA051578-15] Funding Source: Medline
Ask authors/readers for more resources
Despite intensive study, the molecular mechanism for cell toxicity of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-bound doxorubicin remains unclear. Moreover, the ability of the released drug to accumulate in the nucleus has also been questioned. We have hypothesized that the pattern of cell cycle progression is a useful indicator for the presence of free doxorubicin in the nucleus and its interaction with nuclear DNA. The effects of HPMA copolymer-bound doxorubicin on cell cycle progression were evaluated in this study in cultured human ovarian cancer A2780 cells. We determined that P-GFLG-DOX, but not P-GG-DOX, initiates cell cycle arrest and nuclear fragmentation in the same manner as free DOX, but with a time-delay. Our data indicate that drug release from the conjugate is required for the apoptotic activity associated with the conjugate. (c) 2007 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available