Features that determine telomere homolog oligonucleotide‐induced therapeutic DNA damage‐like responses in cancer cells

Journal of Cellular Physiology - Tập 210 Số 3 - Trang 582-595 - 2007
Norio Ohashi1, Mina Yaar2, Mark S. Eller2, Francesca Truzzi2, Barbara A. Gilchrest2
1Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts 02118-2394, USA.
2Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts

Tóm tắt

AbstractCancer 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 ≥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. J. Cell. Physiol. 210: 582–595, 2007. © 2006 Wiley‐Liss, Inc.

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Journal of Cellular Physiology

Tập 210 Số 3

582-595

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