The anticancer mode of action of the quinone natural product cribrostatin 6

Cribrostatin 6 is a quinone-containing natural product that induces the death of cancer cell lines in culture, but its mechanism of action and scope of activity are unknown. Quinone based drugs have shown potential in the clinic, making cribrostatin 6 an interesting compound to study. The mode of action of cribrostatin 6 is investigated herein. Through a variety of experiments including cell cycle analysis, transcript profiling, and analysis of reactive oxygen species (ROS) production, a hypothesis for the mode of action of cribrostatin 6 is developed. ROS generation is likely the primary mechanism by which cribrostatin 6 induces apoptosis in cancer cells. The synthesis of cribrostatin 6 derivatives was undertaken using a previously published synthesis as inspiration. The cytotoxicity of the derivatives in cancer cell lines was determined, and several derivatives are equally as potent as cribrostatin 6. Given the success of certain ROS producers as anti-cancer agents, cribrostatin 6 and its derivatives have potential as novel chemotherapeutic agents.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2010

Author dc:creator

• Hoyt, Mirth T.

Contributors dc:contributor

• Hergenrother, Paul J.
• Zimmerman, Steven C.
• Baranger, Anne M.
• Katzenellenbogen, John A.

• quinone
• anticancer
• cribrostatin 6
• Reactive oxygen species (ROS)

Statement dc:rights

• Copyright 2010 Mirth T. Hoyt

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/15525

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/15525