Drug Isolated from Chinese Medicinal Plant Blocks RNA Synthesis

In the current study investigators at Johns Hopkins University (Baltimore, MD, USA) worked with cultures of HeLa cells, on which they tested triptolide's effect on different proteins involved with gene control by looking at how much new DNA, RNA, and protein were made by the cells.

They reported in the March 2011 issue of the journal Nature Chemical Biology that triptolide almost immediately blocked manufacture of new RNA while taking much longer to have an effect on the levels of newly made proteins or DNA.

They found that triptolide bound covalently to the protein XPB (also known as ERCC3 or excision repair cross-complementing rodent repair deficiency, complementation group 3 xeroderma pigmentosum group B complementing), a subunit of the transcription factor TFIIH. This binding inhibited XPB's DNA-dependent ATPase activity, which led to the inhibition of RNA polymerase II (RNAPII)–mediated transcription and likely nucleotide excision repair. The identification of XPB as the target of triptolide accounted for the majority of the drug's known biological activity.

"Extracts of this medicinal plant have been used to treat a whole host of conditions and have been highly lauded for anti-inflammatory, immunosuppressive, contraceptive, and antitumor activities," said senior author Dr. Jun O. Liu, professor of pharmacology and molecular sciences at Johns Hopkins University. "We have known about the active compound, triptolide, and that it stops cell growth, since 1972, but only now have we figured out what it does.”

"Triptolide's general ability to stop RNAPII activity explains its anti-inflammatory and anticancer effects," said Dr. Liu. "And its behavior has important additional implications for circumventing the resistance that some cancer cells develop to certain anticancer drugs. We are eager to study it further to see what it can do for future cancer therapy.”

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