Related Experiment Video

Updated: Jul 3, 2026

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
08:34

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer

Published on: April 13, 2015

KML001 cytotoxic activity is associated with its binding to telomeric sequences and telomere erosion in prostate

Pornima Phatak1, Fangping Dai, Melody Butler

  • 1Department of Pharmacology, Cytogenetics Laboratory, University of Maryland, Baltimore, MD, USA.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|July 17, 2008
PubMed
Abstract

Insights

Sodium metaarsenite (KML001) targets short telomeres in cancer cells, causing DNA damage and erosion. This arsenic compound shows potential for treating tumors with critically short telomeres.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • KML001 (sodium metaarsenite) is an orally bioavailable arsenic compound undergoing clinical trials for prostate cancer.
  • Understanding the mechanism of action of KML001 is crucial for its therapeutic development.

Purpose of the Study:

  • To elucidate the mode of action of KML001.
  • To investigate the effects of KML001 on telomerase and telomeres in cancer cells.

Main Methods:

  • Compared KML001 cytotoxicity with telomere length in human solid tumor cell lines.
  • Assessed KML001 binding to telomeres using mass spectrometry.
  • Investigated KML001 effects in relation to reactive oxygen species (ROS) and DNA damage.

Main Results:

  • A strong inverse correlation (r(2) = 0.9) was observed between telomere length and KML001 cytotoxicity.
  • KML001 binds directly to telomeric sequences, causing telomerase translocation and telomere erosion.
  • Telomere targeting and subsequent DNA damage by KML001 were observed specifically in cancer cells with short telomeres.

Conclusions:

  • KML001 functions as a telomere-targeting agent.
  • KML001 demonstrates potential for treating tumors characterized by short telomeres.

More Related Videos

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics06:00

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

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...
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...
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.
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...