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

Hoyt, Mirth T.

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https://hdl.handle.net/2142/15525 Copy

Description

Title

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

Author(s)

Hoyt, Mirth T.

Issue Date

2010-05-14T20:44:14Z

Director of Research (if dissertation) or Advisor (if thesis)

Hergenrother, Paul J.

Doctoral Committee Chair(s)

Hergenrother, Paul J.

Committee Member(s)

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

Department of Study

Chemistry

Discipline

Chemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

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

Abstract

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.

Graduation Semester

2010-5

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

Copyright and License Information

Copyright 2010 Mirth T. Hoyt

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