Features | Partner Sites | Information | LinkXpress
Sign In
BioConferenceLive
JIB
GLOBETECH PUBLISHING

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: Microcomputed tomography images (top) and histology images (bottom) of the knees of mice fed a very high fat diet containing omega-3 fatty acid supplement (left) or only omega-6 fatty acids (right) after a knee injury. The omega-6 diet showed abnormal bone remodeling and calcified tissue formation in the joint (white arrow). The omega-6 diet also showed significant loss of cartilage (red staining, yellow arrowhead) and increased joint inflammation (Photo courtesy of Duke University).

Dietary Omega-3 Fatty Acids Moderate Severity of Osteoarthritis in a Mouse Model

Researchers working with an osteoarthritis (OA) obese mouse model found that the fat content of the animals' diet contributed more to the development or arrest of OA than did body weight.... Read more

Therapeutics

view channel

Vaccine Being Developed for Heart Disease Close to Reality

The world’s first vaccine for heart disease is becoming a possibility with researchers demonstrating significant arterial plaque reduction in concept testing in mice. Klaus Ley, MD, from the La Jolla Institute for Allergy and Immunology (LA Jolla, CA, USA), and a vascular immunology specialist, is leading the vaccine... Read more

Business

view channel

A Surge in IPOs Revitalize Investments for the Global Pharma and Biotech

Anti-infective drugs, oncology, and pharmaceutical contract laboratories attract the most investment up to now. The intensified private equity and venture capital (PEVC) deal activity in the global healthcare industry during the recession years, 2008–2010, witnessed a waning post-2010. However, the decline in deals... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.