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Curry-derived molecules might be too spicy for colorectal cancers

Findings from the AACR Centennial Conference on Translational Cancer Medicine: From Technology to Treatment Singapore, Nov. 4-8, 2007

Curcumin, the yellowish component of turmeric that gives curry its flavor, has long been noted for its potential anti-cancer properties. Researchers from Tohoku University in Sendai, Japan, report on an apparent improvement upon nature: two molecular analogues of curcumin that demonstrate even greater tumor suppressive properties. The team presented their findings from the first test of these molecules in a mouse model of colorectal cancer today at the American Association for Cancer Research Centennial Conference on Translational Cancer Medicine.

According to Tohoku University researcher Hiroyuki Shibata, M.D., curcumin is one of the most widely studied plant-based chemicals with anti-cancer properties. Research has associated curcumin with several distinct actions, including the suppression of genes that promote cell growth (for example, the destruction of the pro-cancerous protein â catenin), and induction of programmed cell death (apoptosis) in colorectal cancer.

Unfortunately, natural curcumin has what researchers term “low bioavailability” -- the molecule quickly loses its anti-cancer attributes when ingested, Shibata says. With the aim of improving the therapeutic potential of curcumin, Shibata and his colleagues synthesized and tested 90 variations of the molecule’s structure. Two, GO-Y030 and GO-Y031, proved to be more potent and bioavailable, than natural curcumin.

“Our new analogues have enhanced growth suppressive abilities against colorectal cancer cell lines, up to 30 times greater than natural curcumin,” said Shibata, associate professor in the Department of Clinical Oncology at the Institute of Development, Aging and Cancer at Tohoku University. “In a mouse model for colorectal cancer, mice fed with five milligrams of GO-Y030 or GO-Y031 fared 42 and 51 percent better, respectively, than did mice in the control group.” In 2006, the researchers published basic safety and structural data for GO-Y030 and GO-Y031 in Molecular Cancer Therapeutics, a publication of the American Association for Cancer Research, and they continue to study the mechanisms behind the molecules’ apparent potencies. In its natural form, the curcumin molecule is composed of two ring structures linked by a chain of seven carbon atoms. The active ring structures of GO-Y030 and GO-Y031, however, are linked by a shorter, five-carbon chain, which Shibata says might – for reasons still under investigation –account for their enhanced potency.

Like curcumin, the researchers believe the new analogues have clinical potential that extends beyond colorectal cancer. “In addition to colorectal cancer, the â catenin-degrading abilities of these molecules could apply to other forms of cancer, such as gastric cancer,” said Shibata. “Like curcumin, these analogues also down-regulate a number of gene products, such as NF-kappa B, ErbB2, K-ras, that are also implicated in breast, pancreas and lung cancers among other diseases.”

“In addition to their chemopreventative abilities, these molecules might also form the basis of a potent chemotherapy, either alone or in combination with other modes of therapy,” said Shibata.

According to Shibata, the next step for the researchers is to further examine the drug delivery mechanisms, toxicology and pharmacokinetics of these analogues, before extending the research to clinical trials. Their studies were funded by the Japanese Society for the Promotion of Science and the Miyagi Health Service Association.

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

The Agency for Science, Technology and Research, or A*STAR, is Singapore's lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based Singapore. A*STAR actively nurtures public sector research and development in Biomedical Sciences, Physical Sciences and Engineering, with a particular focus on fields essential to Singapore's manufacturing industry and new growth industries. It oversees 14 research institutes and supports extramural research with the universities, hospital research centres and other local and international partners. At the heart of this knowledge intensive work is human capital. Top local and international scientific talent drive knowledge creation at A*STAR research institutes. The Agency also sends scholars for undergraduate, graduate and post-doctoral training in the best universities, a reflection of the high priority A*STAR places on nurturing the next generation of scientific talent.

The Genome Institute of Singapore (GIS) is a member of the Agency for Science, Technology and Research (A*STAR). It is a national initiative with a global vision that seeks to use genomic sciences to improve public health and public prosperity. Established in 2001 as a centre for genomic discovery, the GIS will pursue the integration of technology, genetics and biology towards the goal of individualized medicine. The key research areas at the GIS include Systems Biology, Stem Cell & Developmental Biology, Cancer Biology & Pharmacology, Human Genetics, Infectious Diseases, Genomic Technologies, and Computational & Mathematical Biology. The genomics infrastructure at the GIS is utilized to train new scientific talent, to function as a bridge for academic and industrial research, and to explore scientific questions of high impact.

Staci Vernick Goldberg | EurekAlert!
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