Features Partner Sites Information LinkXpress
Sign In
Demo Company

Safe, Low Doses of Highly Toxic Anticancer Drugs Effectively Block Tumor Growth

By BiotechDaily International staff writers
Posted on 12 Apr 2012
Print article
Low doses of two highly toxic anticancer drugs have been shown to effectively inhibit tumor development by removing methyl groups from DNA and thereby activating genes that prevent cancerous growth.

The two drugs are azacitidine and the closely related decitabine. These drugs hypomethylate DNA by inhibiting the enzyme DNA methyltransferase. In the presence of azacitidine methyltransferases incorporate the drug into DNA during replication and into RNA during transcription in the cell. Azacitidine acts as a false substrate and potent inhibitor of methyltransferases leading to reduction of DNA methylation - affecting the way cell regulation proteins are able to bind to the DNA/RNA substrate. Inhibition of DNA methylation occurs through the formation of stable complexes between the molecule and DNA methyltransferases, thereby saturating cell methylation machinery. Decitabine functions in a similar manner to azacitidine, although decitabine can only be incorporated into DNA strands while azacitidine can be incorporated into both DNA and RNA chains.

Investigators at Johns Hopkins University (Baltimore, MD, USA) worked with six leukemia cell lines, seven leukemia patient samples, three breast cancer cell lines, seven breast tumor samples (including four samples of tumors that had spread to the lung), one lung cancer cell line, and one colon cancer cell line. They treated cultures of these cell lines with low-doses of the drugs for three days and then allowed the drug-treated cells to rest for a week. Treated cells and tumor samples were injected into mice, and tumor development was observed for up to 20 weeks.

Results published in the March 16, 2012, issue of Cancer Cell revealed that transient exposure of cultured and primary leukemic and epithelial tumor cells to clinically relevant nanomolar doses of the drugs did not cause immediate cytotoxicity. Nonetheless, this treatment produced an antitumor memory response, including inhibition of subpopulations of cancer stem-like cells. These effects are accompanied by sustained decreases in genomewide promoter DNA methylation, gene reexpression, and antitumor changes in key cellular regulatory pathways. While effects varied among individual tumor cell lines, in general cancer cells reverted to a more normal state and eventually died.

“Low doses of azacitidine and decitabine may reactivate genes that stop cancer growth without causing immediate cell killing or DNA damage,” said contributing author Dr. Stephen Baylin, professor of oncology at Johns Hopkins University. “Our findings match evidence from recent clinical trials suggesting that the drugs shrink tumors more slowly over time as they repair altered mechanisms in cells and genes return to normal function, and the cells may eventually die.”

Related Links:
Johns Hopkins University

Print article



view channel
Image: Cryoelectron micrograph reconstruction of the Chikungunya virus (Photo courtesy of the Washington University School of Medicine).

Broadly Neutralizing Antibodies Protect Mice from Alphavirus Infection

While screening a panel of mouse and human monoclonal antibodies (MAbs) that had been raised against Chikungunya virus, researchers identified several with inhibitory activity against multiple other arthritogenic... Read more


view channel

Molecular Light Shed on “Dark” Cellular Receptors

Scientists have created a new research tool to help find homes for orphan cell-surface receptors, toward better understanding of cell signaling, developing new therapeutics, and determining causes of drug side-effects. The approach may be broadly useful for discovering interactions of orphan receptors with endogenous, naturally... Read more

Lab Technologies

view channel
Image: The new ambr 15 fermentation micro-bioreactor system was designed to enhance microbial strain screening applications (Photo courtesy of Sartorius Stedim Biotech).

New Bioreactor System Streamlines Strain Screening and Culture

Biotechnology laboratories working with bacterial cultures will benefit from a new automated micro bioreactor system that was designed to enhance microbial strain screening processes. The Sartorius... Read more


view channel

Purchase of Biopharmaceutical Company Will Boost Development of Nitroxyl-Based Cardiovascular Disease Drugs

A major international biopharmaceutical company has announced the acquisition of a private biotech company that specializes in the development of drugs for treatment of cardiovascular disease. Bristol-Myers Squibb Co. (New York, NY, USA) has initiated the process to buy Cardioxyl Pharmaceuticals Inc. (Chapel Hill, NC, USA).... Read more
Copyright © 2000-2015 Globetech Media. All rights reserved.