Nutrition and the Prevention and Treatment of Cancer: Association of Cytochrome P450 CYP1B1 With the Role of Fruit and Fruit Extracts

Abstract

Recommendations for a healthy or prudent diet include a large number of daily servings of fruits and vegetables, and these 2 classes of food are widely believed to assist in cancer prevention. One potential mechanism that is rarely mentioned in nutritional studies involves the cytochrome P450 enzyme CYP1B1, which appears to have the unique properties of being a universal cancer marker overexpressed in cancer cells and having the capability of converting various phytochemicals and synthetic chemicals into substances cytotoxic to these cells. Although these particular features of CYP1B1 have not gone unnoticed, there has been relatively little research aimed at exploiting them. Furthermore, therapeutic and preventive strategies currently being considered based on vaccines against the enzyme or inhibition without the generation of cytotoxins can be questioned because they do not take advantage of the unique properties of this enzyme. In addition, a few relevant case histories have been published that use specially designed fruit extracts containing substrates with demonstrated cytotoxic metabolic products, and these reports provide an initial confirmation of the potential of exploiting the unusual properties of this enzyme for cancer therapy.

Paradoxic effects of metformin on endothelial cells and angiogenesis

“…Human CYP1B1 has been reported to metabolize a number of endogenous compounds and is also involved in estrogen metabolism. There are numerous reports on CYP1B1 overexpression in tumor cells (48,49), yet there are few studies on endothelial cell CYP1B1. P450 (CYP) enzymes utilize endogenous substrates, such as arachidonic acid, to generate intracellular second messengers with important roles in vascular function (50).…”

“…Exposure of endothelial cells to other chemopreventive agents, such as phytochemicals, for instance resveratrol (52), also decreases CYP1B1 expression. CYP1B1 has also been suggested to be involved in generating metabolites of phytochemicals that are toxic to tumor cells (48). We postulate that reduction of CYP1B1 could be a leading mechanism of the antiangiogenic effects of metformin.…”

Age-related changes in the mRNA levels of CYP1A1, CYP2B1/2 and CYP3A1 isoforms in rat small intestine

“…The activity of this important system can be changed by inhibition or induction of the enzymes by the numerous drugs and other compounds that occur in the food, e.g., in fruits, herbs, vegetables as well as in either alcoholic or soft beverages (Ware 2009;Nekvindova and Anzenbacher 2007;Hidestrand et al 2005;Fujita 2004). From the medical viewpoint, it is essential that these universally used substances do not cause failure of therapies causing serious health alterations.…”

Rapid Determination of Ginkgolic Acids in Ginkgo biloba Leaf Using Online Column Switching High-Performance Liquid Chromatography-Diode Array Detection and Confirmation by Liquid Chromatography-tandem Mass Spectrometry

“…3,4 However, alkylphenols (ginkgolic acids, ginkgols, and bilobols) contained in the extract are categorized as hazardous constituents because they have allergenic, cytotoxic, mutagenic, and slight neurotoxic properties. 5,6 In particular, draft monographs by the 1999 US and European Pharmacopeias recommend that ginkgolic acids (GAs) be limited to 5 ppm, and this recommendation is followed by most manufacturers.…”