Dihydromethysticin (DHM) for Lung Cancer Chemoprevention

The Division of Cancer Prevention (DCP) is the division of the National Cancer Institute (NCI) devoted to cancer prevention research. DCP provides funding and administrative support to clinical and laboratory researchers, community and multidisciplinary teams, and collaborative scientific networks.

The National Cancer Institute, part of the National Institutes of Health (NIH), is the USA's federal government's principal agency for cancer research and training. NCI's mission is to lead, conduct, and support cancer research across the nation to advance scientific knowledge and help all people to live longer, healthier lives. NCI's scope of work spans a broad spectrum of cancer research across a variety of disciplines and supports research training opportunities at career stages across the academic continuum.

Lung cancer causes ~160,000 deaths annually in the U.S. and prevention will be crucial to win the war on this deadliest cancer. Since DNA modification by tobacco carcinogens is one major driver for lung cancer initiation, blocking DNA adduct formation (the root cause) is a plausible strategy. This proposal focuses on the preclinical studies of dihydromethysticin (DHM) as a novel and highly efficacious chemopreventive agent that inhibits lung tumor initiation via preventing tobacco carcinogen-induced DNA modification. Preliminary data demonstrate that DHM (given during carcinogen exposure period at a dose of 50 ppm in diet) completely blocked NNK-induced lung tumor formation in A/J mice. A natural analog, dihydrokavain (DHK), was completely inactive even at 500 ppm in diet. Such a sharp in vivo difference suggests a crucial role of methylenedioxy functional group for specific targeting by DHM.
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