Date of Award

8-2011

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Legacy Department

Microbiology

Advisor

Larcom, Lyndon L

Committee Member

Eggert , Julia A

Committee Member

Wheeler , Alfred

Committee Member

Tzeng , Jeremy

Abstract

There is an abundance of research correlating diets rich in fruits and vegetables to the reduction or prevention of chronic diseases such as cancer and cardiovascular disease. Plants extracts have also been claimed to possess antiviral, antibacterial, and immunological properties. This study focused on the in vitro and in vivo effects of a water extract from lyophilized Meeker red raspberries on tumor cell viability and immune parameters. A large number of studies have demonstrated the cytotoxic effect of different fruit juices and extracts against tumor cell lines in vitro. However, studies also show that the blood plasma levels of berry phytochemicals are several orders of magnitude lower than the levels which have activity in vitro. This study was undertaken as an attempt to reconcile these apparently contradictory observations and test the value of a novel system for detecting the effect of berry consumption in humans. Subjects who consumed berries donate blood which is tested in vitro. An extract of Meeker red raspberries was tested for its activity against 5 tumor cell lines. Berries from the same lot were consumed by test subjects and their plasma and white blood cells were tested for changes in several immune parameters.
The extract exhibited a potent cytotoxic effect on a variety of cancer cells in vitro; including cells from gastric, prostate, colon, and breast cancers. By comparison to an ascorbic acid control, it could be determined that the cytotoxicity of the raspberry extract was not solely attributable to pH or antioxidant effects.
The goal of the present study was to evaluate the effects of lyophilized red raspberry consumption on in vivo and in vitro immune parameters, including immune cell proliferation, plasma MMP-9 concentrations, and cytotoxicity toward human tumor cell lines.
Sixteen healthy volunteers participated in the 3.5 day study. Venous blood samples were collected at baseline and after the last serving of berries. Although much variability was observed among participants, our results suggest that raspberry phytochemicals might augment immune function and affect both the innate and adaptive immune responses in some individuals, but have minimal effects in others.
In several of the participants, the levels of one or more subsets of leukocytes changed after berry intake. In five donors mitogen-induced T lymphocyte proliferation increased and in five it decreased. An inverse relationship was observed between T lymphocyte mitogen stimulation and the change in leukocyte levels. There was an increase in resting peripheral blood mononuclear cell metabolism, suggesting an in vivo priming or proliferative effect from the berry phytochemicals. Changes in plasma levels of MMP-9 correlated with changes in leukocyte levels.
In vitro plasma tumoricidal activity increased for all participants. An increase in peripheral blood mononuclear cell cytotoxicity was also observed in some donors. The results demonstrate that consumption of raspberry phytochemicals can affect immune parameters measured in vitro and may affect responses of the host to pathogenic challenge.

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