The effect of doxorubicin on the U2OS cell cycle

Treatment of U20S cells with the chemotherapeutic drug Doxorubicin results in either apoptosis or cellular senescence. The pathway the cell takes is dependent upon the dosage of Doxorubicin administered to the cells. When a 10 [mu]M dose is administered Topoisomerase II is inhibited resulting in double stranded DNA breaks because the DNA is unable to relegate during synthesis. This is shown by lower levels of synthesis after analysis with Bro mo-2-deoxyuridine (BrdU) and Propidium Iodide (PI) staining. The cells are unable to recover from the severity of this damage and become apoptotic. When a 2 [mu]M dose is applied to the cells, a G2 arrest occurs. This is shown by lower levels of Cyclin B in the G2 phase during flow cytometry analysis and staining with PI. Apoptosis levels are monitored using cleaved Caspase 3 and cleaved PARP. The percentage of 10 [mu]M cells undergoing apoptosis increased steadily over 48 hours, while the 2 [mu]M and untreated cells maintained constant low levels of apoptosis. Both cellular senescence and apoptosis put a halt to cell proliferation.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Mechanical Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2008

Author dc:creator

• Weston, Katherine D

Advisor dc:contributor.advisor

• Gerard Ostheimer and Nicholas G. Hadjiconstantinou.

• Mechanical Engineering.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/45265

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/45265