Dietary Supplements and Gene Therapy Protects Mice from Pancreatic Cancer

Cancer researchers have combined gene therapy with a dietary supplement in a novel chemoprevention gene therapy (CGT) approach to treat or prevent pancreatic cancer.

Pancreatic cancer is one of the deadliest of cancers, so that even with aggressive therapy, the five-year survival rate is less than five percent. Pancreatic cancer cells are resistant to most types of classical chemotherapy as well as to new immunochemical agents such as the cytokine melanoma differentiation associated gene-7/interleukin-24, (mda-7/IL-24).

In the current study, investigators at Virginia Commonwealth University (Richmond, USA; www.vcu.edu) sought a method to counter the resistance, due to a "protein translational block,” of pancreatic cancer cells to mda-7/IL24. Using a mouse model of human pancreatic cancer, they treated the animals with the dietary supplement perillyl alcohol (POH) before using a viral vector to transfect them with the gene for mda-7/IL24.
Perillyl alcohol is a cyclic monoterpene derived from essential oils in various plants including lavender, peppermint, cherries, sage, and lemongrass. It has been shown to cause G1 cell cycle arrest, induce apoptosis, and inhibit posttranslational modification of signal transduction proteins.

Results published in the July 2008, issue of the journal Molecular Cancer Therapeutics revealed that the combination of POH and adenovirus-transmitted cytokine efficiently abrogated the mda-7/IL-24 protein translational block that protected the cancer cells from the effects of MDA-7/IL24, resulting in MDA-7/IL-24 protein production and growth suppression. The CGT approach not only prevented pancreatic cancer growth and progression in the mice, but it also effectively killed established tumors.

"Our hypothesis was that certain nontoxic dietary agents that had the ability to promote reactive oxygen species (ROS) would break down pancreatic cancer cell resistance to therapy following administration of mda-7/IL-24 and be safe for human use,” said senior author Dr. Paul B. Fisher, professor of human and molecular genetics at Virginia Commonwealth University. "We are very excited at the prospect of this chemoprevention gene therapy as a means of both preventing and treating pancreatic cancer, and it has significant potential to move rapidly into human clinical trials.”

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