Tandem Treatment Blocks Growth of Pancreatic Cancer Stem Cells

The drug sorafenib, which is already in use for the treatment of kidney and some forms of liver cancer, has been shown to block effectively the growth of pancreatic cancer stem cells, especially when used in tandem with the broccoli isothiocyanate sulforaphane.

Investigators at the Heidelberg University Hospital (Germany) worked with cultures of pancreatic stem cells as well as with an immunodeficient mouse model. They reported in the June 8, 2010, online edition of the journal Cancer Research that sorafenib treatment diminished the tendency of the cancer stem cells to form clones and spheroids. The drug also inhibited aldehyde dehydrogenase 1 (ALDH1) activity, growth in immunodeficient mice, proliferation, and angiogenesis and induced apoptosis. On the other hand, the drug was observed to induce activation of NF-kappaB, which is associated with survival and re-growth of spheroids.

To counter NF-kappaB activation the investigators co-treated the cultures with the known NF-kappaB inhibitor, sulforaphane, a naturally occurring component of broccoli and similar plants. They found that this tandem treatment eliminated NF-kappaB activity, which was evidenced by the synergistic reduction of tumor size in the immunodeficient mouse model. At the molecular level, reduction in tumor size was due to induction of apoptosis and the inhibition of cell proliferation and angiogenesis.

"We assume that nutrition may be a suited approach to break therapy resistance of cancer stem cells and thus make tumor treatment more effective,” said senior author Dr. Ingrid Herr, professor of molecular oncosurgery at Heidelberg University Hospital.

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