HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 38, 35968-35978, September 19, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/38/35968    most recent M303280200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rajesh, D. Articles by Howard, S. P. Search for Related Content PubMed PubMed Citation Articles by Rajesh, D. Articles by Howard, S. P. Social Bookmarking                      What's this?

Perillyl Alcohol as a Radio-/Chemosensitizer in Malignant Glioma^*

Deepika Rajesh , Rachelle A. Stenzel  and Steven P. Howard  ¶

From the Department of Human Oncology, University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin 53792 and the Department of Bacteriology, Madison, Wisconsin 53706

The prognosis for patients with malignant glioma has not significantly changed in two decades, despite advances in surgery, radiation, and chemotherapy, emphasizing the growing need for novel approaches to glioma therapy. Perillyl alcohol (POH) is a naturally occurring monoterpene that has been shown to possess chemotherapeutic as well as chemopreventive activity in animal tumor models and is currently in Phase I and Phase II clinical trials. In the present study, we have demonstrated that POH is an effective radiosensitizer at clinically relevant doses of radiation using established glioma cell lines. POH caused a transient arrest in the G₂/M phase of the cell cycle and induced apoptosis in glioma cells. POH treatment sensitized glioma cells to Fas-mediated apoptosis, which was further augmented in the presence of ionizing radiation and abrogated in the presence of antagonistic antibody. POH-induced radiosensitization was partially inhibited in glioma cells expressing dominant negative Fas-associated death domain and completely inhibited in glioma cells overexpressing the cytokine response modifier A. In addition, POH treatment resulted in a dose-dependent sensitization to cisplatin and doxorubicin induced cytotoxicity in glioma cells, highlighting its usefulness as a potent radio/chemosensitizer in the treatment of malignant glioma.

Received for publication, March 31, 2003 , and in revised form, June 11, 2003.

^* This work was supported by start up funds from the University of Wisconsin Comprehensive Cancer Center (to S. P. H.), American Cancer Society Grant IRG-58-011-42, and Radiological Society of North America Grant SD0027. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ To whom correspondence should be addressed: K4/354, CSC, 600 Highland Ave., Madison, WI 53792. Tel.: 608-262-8649; Fax: 608-263-9947; E-mail: howard{at}mail.humonc.wisc.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H. Loutrari, M. Hatziapostolou, V. Skouridou, E. Papadimitriou, C. Roussos, F. N. Kolisis, and A. Papapetropoulos Perillyl Alcohol Is an Angiogenesis Inhibitor J. Pharmacol. Exp. Ther., November 1, 2004; 311(2): 568 - 575. [Abstract] [Full Text] [PDF]