Chuu, Jones and their colleagues ran micro-western arrays to assess the impact of CAPE treatment on the proteins of cellular pathways involved in cell growth -- experiments that would have been prohibitively expensive without the new technique.

"What this allowed us to do is screen about a hundred different proteins across a broad spectrum of signaling pathways that are associated with all sorts of different outcomes. You can pick up all the pathways that are affected and get a global landscape view, and that's never been possible before," Jones said. "It would have taken hundreds of Westerns, hundreds of technicians, and a very large amount of money for antibodies."

The micro-western array results allowed researchers to quickly build a new model of CAPE's cellular effects, significantly expanding on previous work that studied the compound's mechanisms. Treatment with CAPE at the concentrations that arrested cancer cell growth suppressed the activity of proteins in the p70S6 kinase and Akt pathways, which are important sensors of sufficient nutrition that can trigger cell proliferation.

"It appears that CAPE basically stops the ability of prostate cancer cells to sense that there's nutrition available," Jones said. "They stop all of the molecular signatures that would suggest that nutrition exists, and the cells no longer have that proliferative response to nutrition."

The ability of CAPE to freeze cancer cell proliferation could make it a promising co-treatment alongside chemotherapies intended to kill tumor cells. Jones cautioned that clinical trials would be necessary before CAPE could be proven effective and safe for this purpose in humans. But the CAPE experiments offer a precedent to unlock the biological mechanisms of other natural remedies as well, perhaps allowing these compounds to cross over to the clinic.
"A typical problem in bringing some of these herbal remedies into the clinic is that nobody knows how they act, nobody knows the mechanism, and therefore researchers are typically very hesitant to add them to any pharmaceutical treatment strategy," Jones said. "Now we'll actually be able to systematically demonstrate the parts of cell physiology that are affected by these compounds."

The paper, "Caffeic acid phenethyl ester suppresses the proliferation of human prostate cancer cells through inhibition of p70S6K and Akt signaling networks," will be published online May 4 by Cancer Prevention Research. In addition to Chuu and Jones, authors include Mark F. Ciaccio, John M. Kokontis, Ronald J. Hause, Jr., Richard A. Hiipakka and Shutsung Liao of the University of Chicago; and Hui-Ping Lin of the National Health Research Institutes in Taiwan.

Research was supported by grants from the Cancer Research Foundation, American Cancer Society, National Institutes of Health, U.S. Department of Health, and National Science Council.