Vitamin D and docosahexaenoic acid inhibit proliferation of the ovarian cancer cell line OVCAR4.

BACKGROUND: Ovarian cancer is one of the deadliest cancers in women. Improved preventative, diagnostic, and therapeutic strategies are needed. Certain dietary patterns and nutrients such as vitamin D and omega-3 fatty acids are associated with reduced cancer risk, but their effects on ovarian cancer remain to be fully elucidated, and their combined effects have not been explored. AIM: To determine the individual and combined effects of the active vitamin D metabolite, calcitriol, and the omega-3 fatty acid, docosahexaenoic acid, on cell growth, and the abundance of the vitamin D receptor (VDR), proteins that modulate cell cycle progression, and apoptotic markers. METHODS: OVCAR4 cells, a model of ovarian cancer, were treated with calcitriol, and docosahexaenoic acid, either alone or in combination. Effects on cell growth were determined by the sulforhodamine B assay. Changes in VDR, the cell cycle promotor c-Myc, the cell cycle inhibitor p27 and cleaved PARP, were determined by Western blotting. RESULTS: While OVCAR4 cell growth was inhibited by individual treatment with either calcitriol or docosahexaenoic acid, the combined treatment revealed enhanced growth inhibition as compared to either treatment alone. Furthermore, long-term treatment (12 days) yielded stronger growth inhibition at lower concentrations as compared to short-term treatments (3 days). Accompanying this growth inhibition was a decrease in c-Myc, and an increase in p27. CONCLUSIONS: The observed reduction in cell growth mediated by calcitriol and docosahexaenoic acid highlights the need for further research utilizing these nutrients, alone and especially in combination, to support ovarian cancer prevention and treatment.

Bone health and osteoporosis: the role of vitamin K and potential antagonism by anticoagulants.

BACKGROUND: Vitamin K's effects extend beyond blood clotting to include a role in bone metabolism and potential protection against osteoporosis. Vitamin K is required for the gamma-carboxylation of osteocalcin. Likewise, this gamma-carboxylation also occurs in the liver for several coagulation proteins. This mechanism is interrupted by coumarin-based anticoagulants in both the liver and bone. METHODS: A thorough review of the literature on vitamin K, osteocalcin and their role in bone metabolism and osteoporosis, as well as the potential bone effects of anticoagulant therapy was conducted. CONCLUSIONS: Epidemiological studies and clinical trials consistently indicate that vitamin K has a positive effect on bone mineral density and decreases fracture risk. Typical dietary intakes of vitamin K are below the levels associated with better BMD and reduced fracture risk; thus issues of increasing dietary intakes, supplementation, and/or fortification arise. To effectively address these issues, large-scale, intervention trials of vitamin K are needed. The effects of coumarin-based anticoagulants on bone health are more ambiguous, with retrospective studies suggesting that long-term therapy adversely affects vertebral BMD and fracture risk. Anticoagulants that do not affect vitamin K metabolism are now available and make clinical trials feasible to answer the question of whether coumarins adversely affect bone. The research suggests that at a minimum, clinicians should carefully assess anticoagulated patients for osteoporosis risk, monitor BMD, and refer them to dietitians for dietary and supplement advice on bone health. Further research is needed to make more efficacious decisions about vitamin K intake, anticoagulant therapy, and bone health.

Flavanols and platelet reactivity.

Platelet activity and platelet-endothelial cell interactions are important in the acute development of thrombosis, as well as in the pathogenesis of cardiovascular disease. An increasing number of foods have been reported to have platelet-inhibitory actions, and research with a number of flavanol-rich foods, including, grape juice, cocoa and chocolate, suggests that these foods may provide some protection against thrombosis. In the present report, we review a series of in vivo studies on the effects of flavanol-rich cocoa and chocolate on platelet activation and platelet-dependent primary hemostasis. Consumption of flavanol-rich cocoa inhibited several measures of platelet activity including, epinephrine- and ADP-induced glycoprotein (GP) IIb/IIIa and P-Selectin expression, platelet microparticle formation, and epinephrine-collagen and ADP-collagen induced primary hemostasis. The epinephrine-induced inhibitory effects on GP IIb/IIIa and primary hemostasis were similar to, though less robust than those associated with the use of low dose (81 mg) aspirin. These data, coupled with information from other studies, support the concept that flavanols present in cocoa and chocolate can modulate platelet function through a multitude of pathways.

The effects of flavanol-rich cocoa and aspirin on ex vivo platelet function.

BACKGROUND: Flavanols modulate platelet function in vitro, but less is known of their in vivo effects and how they compare to pharmacological platelet inhibitors. We investigated the effect of a flavanol-rich cocoa beverage (897 mg/ml) in combination with and in comparison to aspirin on platelet function and activation in healthy subjects. METHODS AND RESULTS: On separate test days in a crossover design, 16 healthy adults consumed aspirin (81 mg), cocoa (as a beverage), or aspirin plus cocoa. Platelet activation was measured by surface expression of P-selectin and PAC-1 binding to the activated conformation of the GPIIb/IIIa receptor (GPIIb/IIIa-act). Platelet function was measured on an analyzer (the PFA-100) that measures shear stress-induced platelet plug formation in response to collagen-epinephrine or collagen-ADP. Plasma epicatechin concentrations peaked approximately 2 h after subjects were given either the cocoa or aspirin plus cocoa. After 6 h, cocoa inhibited epinephrine-induced platelet function. Epinephrine-induced platelet function was inhibited 2 and 6 h after aspirin, and after aspirin plus cocoa. Epinephrine-stimulated P-selectin expression was inhibited by aspirin at 6 h, and after 2 and 6 h by aspirin plus cocoa. ADP-stimulated P-selectin expression was not affected by the treatments. Cocoa and aspirin, given separately, reduced epinephrine-stimulated GPIIb/IIIa-act expression at 2 and 6 h, respectively, and at 2 and 6 h when given together, suggesting an additive effective. ASA plus cocoa inhibited ADP-stimulated GPIIb/IIIa-act expression at 6 h. CONCLUSIONS: Flavanol-rich cocoa inhibited epinephrine-stimulated platelet activation and function. These effects were qualitatively similar to aspirin, but less profound. These results emphasize the need to further examine the effects of food flavonoids for platelet modulating effects.