Peter Ferguson, PhD

Peter Ferguson, PhD

Biography

Dr. Peter Ferguson graduated in 1979 from Dalhousie University, Halifax, Nova Scotia with an Honours Degree in Biochemistry. He earned a Ph. D. in 1985 from the University of Alberta, supervised by Dr. Carol Cass in the Cancer Reseach Group and the Department of Biochemistry. Following a post-doctoral fellowship with Dr. Yung-chi (Tommy) Cheng in the Department of Pharmacology at the University of North Carolina (Chapel Hill), Pete took a faculty position in the Department of Otolaryngology and Lawson Research Institute at the University of Western Ontario (UWO), London, Canada.  Pete has performed teaching for the Department of Physiology and Pharmacology since 1985, and, following a move to the London Regional Cancer Centre in 1996, is now a Research Associate and Adjunct Professor in the Department of Oncology of UWO and London Health Sciences Centre.

Dr. Ferguson’s research interests include isolating and characterizing anticancer activity of cranberry extracts. His group was the first to demonstrate that tumour growth in mice could be inhibited by treatment of the animals (intraperitoneal injection) with a semi-purified extract of cranberry. This extract, rich in flavonoids and other polyphenolic phytochemicals, is being further characterized to identify the active anticancer component(s).  Another research interest is the use of antisense technology to sensitize cancer cells to chemotherapy drugs.  Dr. Ferguson and colleagues were the first to demonstrate the use of an antisense molecule to down-regulate a drug target (thymidylate synthase) to sensitize cancer cells to a specific drug (5-fluorodeoxyuridylate and pemetrexed).  Dr. Ferguson also works on other small molecule chemosensitizers.

Pete is married (Susan) and has 2 children (Ryan, 21, Lindsay, 18).  He enjoys hiking, photography, hockey, guitar and bicycling. He is a member of the London Terry Fox Run organizing committee, and coaches minor hockey.

Abstract

Cranberry Phytochemicals as Potential Anticancer Agents

Cancer chemotherapy, in combination with other therapies, has been successful in retarding cancer progression and effecting cures. However, approximately 50% of cancers are not cured and improvement is needed. Given the limitations to cancer chemotherapy and the association of diets high in fruits and vegetables with lower cancer risk, edible foodstuffs have been investigated as a source of compounds, or phytochemicals, to both prevent cancer and treat established tumors.

Although phytochemicals are comprised of many subclasses, the most commonly identified anticancer phytochemicals include, but are not limited to, flavonoids. Flavonoids themselves are a family of over 5000 distinct compounds, each with a 3_ring, heterocyclic structure containing hydroxyl and keto groups in various states of methylation and conjugation with other compounds. The many oxygen moieties contribute to the ubiquitous activity of flavonoids as antioxidants.

However, many flavonoids and other phytochemicals also interact with cellular molecules to influence activities that control various biological functions ranging from proliferation and survival, to angiogenesis, to drug metabolism. Modulation of each of these processes can influence tumor progression, and all are potential targets for treatment of tumors. Flavonoids isolated from various sources including apples (quercetin) and green tea [epigallocatechin gallate (EGCG)] are known to retard or abrogate cancer cell proliferation. Among numerous examples of their anticancer activity, quercetin and EGCG inhibit in vivo growth of colon (1) and pancreatic (2) tumor explants, respectively, in mice.

Due to their very high flavonoid content, edible berries have become the focus of widespread investigation of anticancer activity. We have investigated cranberries (Vaccinia macrocarpa) as a source of components with potential as chemotherapeutic and/or cancer preventive agents. Flavonoid_containing cranberry extracts referred to as Fraction 6 (Fr6) and proanthocyanidins (PACs) demonstrated antiproliferative activity against eight different human cancer cell lines in vitro, resulting from both cell cycle inhibition/arrest and induction of apoptosis (3). Cranberry extracts also inhibited growth of human tumor cell line explants in vivo when administered by intraperitoneal injection to tumor_bearing mice (4). Further chromatographic fractionation of the crude flavonoid isolates from cranberry has yielded antiproliferative fractions containing a small number of discrete constituents. Individual compounds responsible for most or all antiproliferative activity have not yet been identified although there are several candidates, based on reported activity of known cranberry constituents.

Crude cranberry extracts and some individual cranberry components display anticancer activity both directly in an antiproliferative and cell-killing action and also in a cancer preventive role (5-28). Components of cranberry with anticancer activity have been identified by other groups. The most abundant components of cranberry known to inhibit cancer cell growth are the flavonoids quercetin and myricetin, mostly in the form of glycosidic, benzoic and cinnamic conjugates (6-21). PACs from cranberry are comprised of non_galloylated polymers of the flavan_3_ol epicatechin of 2 to 12 degrees of polymerization (29-32), which have antiproliferative activity (7, 8, 11, 22). Three triterpene hydroxycinnamates, non_flavonoids isolated from cranberry, also have antiproliferative activity (23). Data on in vivo anticancer activity of cranberry phytochemicals, either as a crude extract (4, 5) or as individual constituents (1, 27, 28), is very limited. Ursolic acid, a triterpenoid pentacyclic compound, and its various conjugates, exist in quantities in cranberry similar to those of flavonoids and inhibit tumor cell line growth both in vivo (27, 28) and in vitro (8).

Other minor components with anticancer activity include resveratrol and possibly hydroxycinnamic acid (8). Quercetin slowed growth of several mouse tumor cell line explants (1) and, in concert with pterostilbene, inhibited growth of melanoma metastases (33) in syngeneic mouse models. Direct in vivo antitumor activity has not been reported for any other cranberry phytochemical. Work is currently underway to identify the components of Fr6 and PACs that contribute to the antitumor activity of these cranberry extracts. In view of the demonstrated in vivo anticancer activity of the crude cranberry extract (4), one or more purified components of cranberry may be useful contributors to cancer prevention and possibly anticancer therapy.