Jing Chen and colleagues at Winship Cancer Institute recently published a paper in Molecular Cell. Most of the paper deals with a metabolic enzyme, 6PGD (6-phosphogluconate dehydrogenase), and how it is more active in cancer cells.
Tucked in at the end is a note that an inhibitor of 6GPD with an odd name, physcion, has anticancer activity in Chen’s team’s hands. Physcion, also known as parietin, is an orange-yellow pigment extractable from lichens and Chinese rhubarb that has been employed as an anti-mildew agent.
Probing cancer cells’ warped metabolism is a promising approach, for both drug discovery and finding effective ways to combine existing drugs, because of the Warburg effect: cancer cells’ tendency to suck up lots of sugar and use it in energy-inefficient ways.
Cancer cells don’t contain more abundant 6GPD, Chen’s team found, but the enzyme is more active because of a protein modification called acetylation. Having more active 6GPD enables part of the cells’ metabolic chain called the pentose phosphate pathway — sort of like cells’ construction industry — to be more productive. That’s helpful if you’re a cancer cell and all you want to do is grow without regard to the consequences.
Chen reports that more information on the anticancer activity of chemical relatives of physcion will be available in an upcoming publication. Co-first authors of the Molecular Cell paper are postdoc Changliang Shan, PhD and graduate student Shannon Elf, now a postdoc at Harvard.
Pictures of Caloplaca lichen and Chinese rhubarb used under Creative Commons license.
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