The 3,4-Quinones of Estrone and Estradiol Are the Initiators of Cancer whereas Resveratrol and N-acetylcysteine Are the Preventers.

Ercole Cavalieri,Eleanor Rogan

doi:10.3390/ijms22158238

Abstract

This article reviews evidence suggesting that a common mechanism of initiation leads to the development of many prevalent types of cancer. Endogenous estrogens, in the form of catechol estrogen-3,4-quinones, play a central role in this pathway of cancer initiation. The catechol estrogen-3,4-quinones react with specific purine bases in DNA to form depurinating estrogen-DNA adducts that generate apurinic sites. The apurinic sites can then lead to cancer-causing mutations. The process of cancer initiation has been demonstrated using results from test tube reactions, cultured mammalian cells, and human subjects. Increased amounts of estrogen-DNA adducts are found not only in people with several different types of cancer but also in women at high risk for breast cancer, indicating that the formation of adducts is on the pathway to cancer initiation. Two compounds, resveratrol, and N-acetylcysteine, are particularly good at preventing the formation of estrogen-DNA adducts in humans and are, thus, potential cancer-prevention compounds.

Highlights

Estrogens play a role in the development of multiple types of prevalent cancers
Similar to the high ratios of estrogen-DNA adducts to estrogen metabolites and conjugates in women at high risk for breast cancer, these results suggest that the formation of estrogen-DNA adducts is a precursor to the development of cancer
The quinones react with DNA to primarily form the depurinating DNA adducts 4-OHE1(E2)-1N7Gua and 4-OHE1(E2)-1-N3Ade

Summary

Introduction

Estrogens play a role in the development of multiple types of prevalent cancers. This relationship has been observed for more than a century. Data support a relationship between levels of circulating estrogens and risk of ovarian or endometrial cancer in postmenopausal women [1]. Aromatase knock-out mice cannot produce E2 in the prostate, and they develop benign prostate hypertrophy rather than prostate cancer [9] All of this information demonstrates the critical role of estrogens in the etiology of prostate cancer. Depurinating estrogen-DNA adducts play a critical role in the etiology of various prevalent types of cancer

Initiation of Cancer

Prevention of Cancer by Inhibition of Estrogen-DNA Adduct Formation

Findings

Conclusions