Abstract |
Cancer is the second leading cause of death in the USA, with metastatic disease proving a particular management challenge. Treatment modalities for patients with metastatic disease are limited, and survival beyond 5 years is uncommon. We have reported that an 11-base DNA oligonucleotide 100% homologous to the telomere 3' overhang can induce apoptosis, senescence and/or differentiation of several types of malignant cells in vitro and in vivo, while having minimal effect on normal cells. We now report that 22 oligonucleotides, 9-20 bases in length, with or without a 5' phosphate group and with varying homology (40-100%) to the 3' overhang, inhibit growth and induce apoptosis of human cell lines derived from breast cancers, pancreatic and ovarian carcinomas, and malignant melanoma, lines that lack p53 and/or p16 and harbor a variety of other abnormalities in key regulatory signaling pathways. Cytosine (C) content adversely affected oligonucleotide efficacy, decreasing their effect on cellular apoptosis by > or =80%. These data confirm and expand our earlier work suggesting that such telomere homolog oligonucleotides (T-oligos) target an innate anti- cancer defense system in human cells and may provide an effective treatment for cancers of multiple different cellular origins and genetic profile.
|
Authors | Norio Ohashi, Mina Yaar, Mark S Eller, Francesca Truzzi, Barbara A Gilchrest |
Journal | Journal of cellular physiology
(J Cell Physiol)
Vol. 210
Issue 3
Pg. 582-95
(Mar 2007)
ISSN: 0021-9541 [Print] United States |
PMID | 17133364
(Publication Type: Journal Article)
|
Copyright | Copyright 2006 Wiley-Liss, Inc. |
Chemical References |
- DNA, Neoplasm
- H2AX protein, human
- Histones
- Oligonucleotides
|
Topics |
- Aging
(drug effects)
- Apoptosis
(drug effects)
- Cell Line, Tumor
- Cell Nucleus
(pathology)
- Cell Proliferation
(drug effects)
- Cell Transformation, Neoplastic
(drug effects)
- DNA Damage
(genetics)
- DNA, Neoplasm
(drug effects, genetics)
- Histones
(metabolism)
- Humans
- Neoplasms
(drug therapy, genetics, pathology)
- Oligonucleotides
(chemistry, genetics, pharmacology)
- Phosphorylation
(drug effects)
- S Phase
(drug effects)
- Telomere
(genetics)
|