Features | Partner Sites | Information | LinkXpress
Sign In
PZ HTL SA
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC

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

By BiotechDaily International staff writers
Posted on 12 Apr 2012
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




comments powered by Disqus

Channels

Genomics/Proteomics

view channel
Image: This novel, flexible film that can react to light is a promising step toward an artificial retina (Photo courtesy of the American Chemical Society).

Novel Nanofilm May Be Artificial Retina Precursor

Researchers have used advanced nanotechnology techniques to develop a light-sensitive film that has potential for future artificial retina applications. Investigators at the Hebrew University of Jerusalem... Read more

Biochemistry

view channel

Blocking Enzyme Switch Turns Off Tumor Growth in T-Cell Acute Lymphoblastic Leukemia

Researchers recently reported that blocking the action of an enzyme “switch” needed to activate tumor growth is emerging as a practical strategy for treating T-cell acute lymphoblastic leukemia. An estimated 25% of the 500 US adolescents and young adults diagnosed yearly with this aggressive disease fail to respond to... Read more

Business

view channel

R&D Partnership Initiated to Reduce Development Time for New Drugs

nanoPET Pharma, GmbH (Berlin, Germany) signed an open-ended framework contract with the international pharmaceutical company Boehringer Ingelheim (Ridgefield, CT, USA). By developing customized contrast agents for research in both basic and preclinical studies, nanoPET Pharma will contribute to the enhancement of Boehringer... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.