Role of Oxidative Stress Response Elements and Antioxidants in Prostate Cancer Pathobiology and Chemoprevention -- A Mechanistic Approach

Suresh   C.   Sikka

Abstract

Prostate cancer (PC) has become the most frequently diagnosed neoplasm and the second leading cause of cancer-related mortality in men. Its incidence rate has continued to increase rapidly during the past two decades, especially in men over the age of 50 years as they are living longer. The prostate in aging males is highly susceptible to benign and malignant proliferative changes. About two / thirds of all cancers, however, could have been prevented based upon lifestyle choices. The preventative and therapeutic options available to men prone to prostate cancer (both benign and malignant) are limited. How environment, diet and genetics interact to either induce or prevent prostate cancer (PC) is not known. Free radicals, called reactive oxygen species (ROS), play a significant but paradoxical role acting as a “double-edged sword” to regulate cellular processes. Recent in vitro studies using benign prostate hyperplasia (BPH) and PC cell lines grown under various oxidative stress conditions confirm this theory. This manuscript describes key signal transduction mechanisms involved in ROS induced effects on prostate cell growth, cell-cycle checkpoints, apoptosis and transcription factors and the role of potential dietary antioxidants on these mechanisms. It is important to understand underlying signaling mechanisms affected by oxidative stress so as to scientifically prove the efficacy and safety of potential antioxidants in PC prevention. Thus by identifying several potential preventive and therapeutic molecular targets in prostate and by devising better chemo-preventive and chemotherapeutic strategies for controlling PC progression, one can envision significant drop in number of deaths, cut down health care costs and improve the quality of life.

Keywords: prostate disease (bph and cancer), aging, reactive oxygen species, oxidative stress, selenium, curcumin, lycopene, mitochondria, caspases, transcription factors