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

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: fj.06-6941comv1 21/11/2918    most recent Alert me when this article is cited Alert me if a correction is posted 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Aoki, H. Articles by Kondo, S. Search for Related Content PubMed PubMed Citation Articles by Aoki, H. Articles by Kondo, S.

Telomere 3' overhang-specific DNA oligonucleotides induce autophagy in malignant glioma cells

Hiroshi Aoki^*,1, Eiji Iwado^*,1, Mark S. Eller, Yasuko Kondo^*, Keishi Fujiwara^*, Guang-Zhi Li, Kenneth R. Hess, Doris R. Siwak, Raymond Sawaya^*,||, Gordon B. Mills, Barbara A. Gilchrest and Seiji Kondo^*,||,¶,2

Department of
^* Neurosurgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA;

Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts, USA; Departments of

Biostatistics and Applied Mathematics and

Molecular Therapeutics, The University of Texas M. D. Anderson Cancer Center;

^|| Department of Neurosurgery, Baylor College of Medicine; and

^¶ The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, USA

²Correspondence: Department of Neurosurgery, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit BSRB 1004, Houston, TX 77030, USA. E-mail: seikondo{at}mdanderson.org.

Telomere 3' overhang-specific DNA oligonucleotides (T-oligos) induce cell death in cancer cells, presumably by mimicking telomere loop disruption. Therefore, T-oligos are considered an exciting new therapeutic strategy. The purpose of this study was to elucidate how T-oligos exert antitumor effects on human malignant glioma cells in vitro and in vivo. We demonstrated that T-oligos inhibited the proliferation of malignant glioma cells through induction of nonapoptotic cell death and mitochondria hyperpolarization, whereas normal astrocytes were resistant to T-oligos. Tumor cells treated with T-oligos developed features compatible with autophagy, with development of autophagic vacuoles and conversion of an autophagy-related protein, microtubule-associated protein 1 light chain 3 from type I (cytoplasmic form) to type II (membrane form of autophagic vacuoles). A reverse-phase protein microarray analysis and Western blotting revealed that treatment with T-oligos inhibited the mammalian target of the rapamycin (mTOR) and the signal transducer and activator of transcription 3 (STAT3). Moreover, pretreatment with T-oligos significantly prolonged the survival time of mice inoculated intracranially with malignant glioma cells compared with that of untreated mice and those treated with control oligonucleotides (P=0.0065 and P=0.043, respectively). These results indicate that T-oligos stimulate the induction of nonapoptotic autophagic also known as type II programmed cell death and are thus promising in the treatment of malignant glioma.—Aoki, H., Iwado, E., Eller, M. S., Kondo, Y., Fujiwara, K., Li, G.-Z., Hess, K. R., Siwak, D. R., Sawaya, R., Mills, G. B., Gilchrest, B. A., Kondo, S. Telomere 3' overhang-specific DNA oligonucleotides induce autophagy in malignant glioma cells.

Key Words: T-oligos • mTOR

This article has been cited by other articles:

				S. Arad, E. Zattra, J. Hebert, E. H. Epstein Jr., D. A. Goukassian, and B. A. Gilchrest Topical Thymidine Dinucleotide Treatment Reduces Development of Ultraviolet-Induced Basal Cell Carcinoma in Ptch-1+/- Mice Am. J. Pathol., May 1, 2008; 172(5): 1248 - 1255. [Abstract] [Full Text] [PDF]