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

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




Channels

Genomics/Proteomics

view channel
Image: Biopsy of small bowel showing celiac disease manifested by blunting of villi, crypt hyperplasia, and lymphocyte infiltration of crypts (Photo courtesy of Wikimedia Commons).

Reduced Elafin Levels Associated with Celiac Disease Bowel Inflammation

Levels of the enzyme elafin, an endogenous serine protease inhibitor, were lower in the small intestinal epithelium of patients with active celiac disease (CD) as compared to similar tissue from control patients.... Read more

Biochemistry

view channel

Mitochondrial Cause of Aging Can Be Reversed

Researchers have found a cause of aging in lab animals that can be reversed, possibly providing an avenue for new treatments for age-related diseases including type 2 diabetes, cancer, muscle wasting, and inflammatory diseases. The researchers plan to begin human trials late 2014. The study, which was published December... Read more

Therapeutics

view channel

Cytokine Identified That Causes Mucositis in Cancer Therapy Patients

The action of the cytokine interleukin 1-beta (IL-1beta) has been found to underlie the onset of mucositis, a common, severe side effect of chemotherapy and irradiation of cancer patients. Mucositis occurs as a result of cell death in reaction to chemo- or radiotherapy. The mucosal lining of the mouth becomes thin, may... Read more

Business

view channel

Analytical Sciences Trade Fair Declared a Rousing Success

Organizers of this year's 24th "analytica" biosciences trade fair have reported significant increases in both the number of visitors and exhibitors compared to the 2012 event. The analytica trade fair for laboratory technology, analysis, and biotechnology has been held at the Munich (Germany) Trade Fair Center every... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.