A plant known as goat’s rue (scientific name Galeaga officinalis), which grows in the United States as well as other parts of the world, may have a role in treating head and neck cancer. In December 1994, the US Food and Drug Administration had approved metformin, a drug modeled after a compound in G officinalis, to treat Type II diabetes. Previous studies have reported that people who control their diabetes with metformin have more than a 40% lower rate of cancer than those who use other diabetes medications. This spawned laboratory work to look for hard-wired explanations written into our cells. Researchers discovered that metformin activates the liver kinase B1-activated protein kinase (LKB1-AMPK) pathway, a molecular choke point that links cell metabolism to growth control and cell polarity. But in turning on LKB1-AMPK, another related cellular pathway known as mammalian target of rapamycin complex 1 (mTORC1) powers down and so does protein synthesis. When that happens, cells lower their energy expenditure and slow their rates of proliferation. Recent work shows that head and neck squamous cell carcinoma (HNSCC) cells commonly turn up mTORC1 to fuel their abnormal growth. Was it possible for metformin to shut down mTORC1 in premalignant HNSCC cells and prevent their progression to metastatic disease?
A team of National Institute of Dental and Craniofacial Research (NIDCR) scientists and colleagues answer in the affirmative in the journal Cancer Prevention Research. The scientists found in a range of standard HNSCC cell lines that metformin prevents their progression, but the compound may do so independently of the LKB1-AMPK. They then showed in mice that metformin acts primarily on the basal proliferating layer of premaliganant lesions, significantly reducing their size and number. The authors concluded, “Collectively, our data underscore the potential clinical use of metformin as a targeted chemopreventive agent in the control of HNSCC development and progression.”
(Source: NIDCR, Science News in Brief, accessed August 17, 2012; Cancer Prevention Research, April 2012, Volume 5, Number 4, pages 562 to 573)
