Inhibition of melanoma angiogenesis by telomere homolog oligonucleotides

Christina Coleman1, Danielle Levine, Raj Kishore

  • 1Department of Dermatology, Boston University School of Medicine, Boston, MA 02118, USA.

Journal of Oncology
|July 24, 2010
PubMed

Insights

Telomere homolog oligonucleotides (T-oligos) demonstrate potent anticancer effects by inhibiting tumor angiogenesis. These T-oligos reduce key proteins involved in blood vessel formation, offering a promising new avenue for melanoma treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Angiogenesis Research

Background:

  • Telomere homolog oligonucleotides (T-oligos) activate innate anticancer responses.
  • T-oligos initiate signaling pathways involving Werner protein and ATM kinase.
  • The antiangiogenic potential of T-oligos remains to be fully elucidated.

Purpose of the Study:

  • To investigate the antiangiogenic effects of T-oligos in melanoma.
  • To determine the molecular mechanisms underlying T-oligo-mediated antiangiogenesis.

Main Methods:

  • Assessed expression of angiogenesis-related factors (VEGF, VEGFR2, angiopoietins) in T-oligo-treated melanoma cells.
  • Evaluated the impact of T-oligos on transcription factors E2F1 and HIF-1alpha.
  • Performed in vitro assays for endothelial cell (EC) tubulogenesis and invasion.
  • Quantified tumor microvascular density in melanoma xenografts following T-oligo administration.

Main Results:

  • T-oligos significantly decreased VEGF, VEGFR2, and angiopoietin expression and secretion.
  • T-oligos activated E2F1 and inhibited HIF-1alpha activity.
  • Inhibition of EC tubulogenesis and invasion was observed in vitro.
  • Systemic T-oligo treatment reduced tumor microvascular density by 60% and functional vessels by 80% in vivo.

Conclusions:

  • T-oligos exhibit significant antiangiogenic properties.
  • The findings support the role of telomere-based responses in restricting tumor angiogenesis.
  • T-oligos represent a potential therapeutic strategy for melanoma treatment by targeting tumor vascularization.

Related Concept Videos

Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...
Telomeres and Telomerase02:41

Telomeres and Telomerase

In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded DNA.
Telomeres and Telomerase02:41

Telomeres and Telomerase

In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded DNA.
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...