Abstract

Ovarian cancer is the sixth most common cancer and accounts for more deaths than any other cancer of the female reproductive system. The American Cancer Society has suggested that poor diet, talc and industrial pollutants may increase the risk of developing ovarian cancer. Talc is ubiquitous and concern is raised about its safety, role as a possible carcinogen and known ability to cause irritation and inflammation. Due to the silent nature of ovarian cancer, chemoprevention is a high priority. The most useful chemopreventive compounds will inhibit, delay or reverse carcinogenesis, and can be taken for long periods of time with no apparent health risk. Pycnogenol® (Pyc), a potent antioxidant, is a proprietary mixture of water-soluble bioflavonoids extracted from the bark of the French maritime pine. In this dissertation, Pyc-induced chemoprevention and talc-induced carcinogenesis of ovarian cancer were explored. Human ovarian cell lines (normal, benign and malignant epithelial; and malignant germ cell) were incubated with 0-500 μg/ml Pyc for 24 hr. Cell viability, apoptosis, reactive oxygen species (ROS) generation and immunodetection of catalase were measured. Pyc was selectively cytotoxic to the malignant germ cells. Basal catalase expression was the lowest in the malignant germ cells and subsequently H2O2 generation was the greatest, corresponding with greater sensitivity to Pyc. Normal human ovarian epithelial and granulosa cell lines and polymorphonuclear neutrophils (PMN) were treated with 0-500 μg/ml talc for up to 120 hr; or 0-500 μg/ml Pyc for 24 hr followed by 5 μg/ml talc for 24 or 72 hr. Cell viability, ROS generation and neoplastic transformation were measured. Talc increased proliferation, induced neoplastic transformation and increased ROS generation time-dependently in the ovarian cells and dose-dependently in the PMN. Pretreatment with Pyc inhibited the talc-induced increase in proliferation, decreased the number of transformed colonies and decreased the ROS generation in the ovarian cells. These results suggest that 1) Pyc is selectively cytotoxic to catalase deficient malignant ovarian germ cells; 2) talc can induce neoplastic transformation in normal ovarian cells, in vitro and 3) Pyc can reduce the talc-induced neoplastic transformation of normal ovarian cells. Thus Pyc may prove to be a potent chemopreventative agent against ovarian carcinogenesis.

LLU Discipline

Microbiology and Molecular Genetics

Department

Microbiology

School

Graduate Studies

First Advisor

Benjamin H.S. Lau

Second Advisor

Penelope Duerksen-Hughes

Third Advisor

Mark S. Johnson

Fourth Advisor

James D. Kettering

Fifth Advisor

Jonathan W. Neidigh

Degree Name

Doctor of Philosophy (PhD)

Degree Level

Ph.D.

Year Degree Awarded

2006

Date (Title Page)

12-2006

Language

English

Library of Congress/MESH Subject Headings

Ovarian Neoplasms -- drug therapy; Antioxidants -- therapy; Pycnogenol -- therapeutic use; Talc -- adverse effects; Carcinogenicity Tests; Risk Factors

Type

Dissertation

Page Count

xiv; 105

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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