Coenzyme Q10 concentrations and antioxidant status in tissues of breast cancer patients

doi:10.1016/S0009-9120(00)00067-9

Clinical Biochemistry

Volume 33, Issue 4, June 2000, Pages 279-284

https://doi.org/10.1016/S0009-9120(00)00067-9 Get rights and content

Abstract

Objectives: An increasing amount of experimental and epidemiological evidence implicates the involvement of oxygen derived radicals in the pathogenesis of cancer development. Oxygen derived radicals are able to cause damage to membranes, mitochondria, and macromolecules including proteins, lipids and DNA. Accumulation of DNA damages has been suggested to contribute to carcinogenesis. It would, therefore, be advantageous to pinpoint the effects of oxygen derived radicals in cancer development.

Design and methods: In the present study, we investigated the relationship between oxidative stress and breast cancer development in tissue level. Breast cancer is the most common malignant disease in Western women. Twenty-one breast cancer patients, who underwent radical mastectomy and diagnosed with infiltrative ductal carcinoma, were used in the study. We determined coenzyme Q10 (Q) concentrations, antioxidant enzyme activities (mitochondrial and total superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase), and malondialdehyde (MDA) levels in tumor and surrounding tumor-free tissues.

Results: Q concentrations in tumor tissues significantly decreased as compared to the surrounding normal tissues (p < 0.001). Higher MDA levels were observed in tumor tissues than noncancerous tissues (p < 0.001). The activities of MnSOD, total SOD, GSH-Px and catalase in tumor tissues significantly increased (p < 0.001) compared to the controls.

Conclusions: These findings may support that reactive oxygen species increased in malignant cells, and may cause overexpression of antioxidant enzymes and the consumption of coenzyme Q10. Increased antioxidant enzyme activities may be related with the susceptibility of cells to carcinogenic agents and the response of tumor cells to the chemotherapeutic agents. Administration of coenzyme Q10 by nutrition may induce the protective effect of coenzyme Q10 on breast tissue.

Introduction

Aerobic metabolism produces reactive oxygen species which have an unpaired electron under physiological conditions 1, 2. Especially in the presence of metal ions, oxygen derived radicals may cause an oxidative damage by reacting with macromolecules including proteins, lipids and DNA in the cell 2, 3. The accumulation of DNA damages has been suggested to contribute to carcinogenesis (3).

Carcinogenesis is a formation, proceeding through at least three different stages including initiation, promotion and malignant conversion, and is significant in human mortality 4, 5. Oxygen derived radicals have been implicated in the etiology of cancer development perhaps since the demonstration that ionizing irradiation caused cancer 3, 6. It has been shown that free radicals have a mutagenic capacity as a result of the interaction between highly reactive chemical molecules and DNA (4). Upon reaction with DNA, oxygen derived radicals produces base adducts and strand breaks. The former can cause mispairing lesions during DNA replication. Those of different types of chemical changes in DNA molecule could be mutagenic lesions involved in the initiation and progression processes of cancer. It was also reported that oxyradicals can also cause cytotoxcity and stimulate changes in gene expression 4, 5, 7.

The cells protect themselves against oxidative damage by enzymatic and nonenzymatic antioxidant systems. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase form primary enzymatic defense system (1). SOD catalyses dismutation of superoxide radicals to hydrogen peroxide. Manganase containing form, MnSOD, is mainly found in mitochondria. Hydrogen peroxide is metabolized by catalase and GSH-Px via reducing into water and molecular oxygen. Another endojen antioxidant is coenzyme Q10 (Q). Q is an essential component and a redox carrier of electrons in the transfer chain in mitochondria (8). It is situated between the flavoprotein complexes and the cytocrome bc1 complex and transfers electrons through protonmotive Q cycle 9, 10. It was shown that the reduced form of Q (QH2) has a powerful antioxidative capacity 8, 9, 10.

The purpose of this study was to examine the relationship between oxidative stress and breast cancer development in tissue level, to analyze antioxidant enzymes and to evaluate the consideration of coenzyme Q10 as chemopreventive agent. Breast cancer is the most common malignant tumor in western women. For this aim, peroxidative damage and antioxidant status in tissue levels were determined in invasive or infiltrative ductal carcinoma (IDC) which represents the most common histological type of breast cancer. Levels of Q in tumor tissues have not been investigated in any breast cancer. So in the present study, Q concentrations and primary defense enzyme activities including total SOD and MnS0D, GSH-Px and catalase were measured. Peroxidative damage was determined by assaying malondialdehyde levels.

Section snippets

Methods

Patients who applied to the Surgical Department at the Medical School of Hacettepe University in the first part of 1996, and underwent a mastectomy with full dissection of axillary lymph nodes, were enrolled in this study. All patients were operated on in the Surgery Department at Hacettepe’s Hospital. Twenty-one women, mean age 44.23 ± 6.13 years, who were histologically diagnosed with primary IDC were included. Patients with a previous carcinoma of the breast, or multiple mammary carcinomas

Results

All carcinomas were classified as infiltrative ductal carcinoma. There were 1 grade I, 4 grade II, and 16 grade III. Axillary lymph node status was known in 10 patients, and metastatic carcinoma was present in one patient. There were 3 multisentric cancer. Vascular invasion was present in one tumor and skin involvement was present in one tumor. Table 1 shows the overall properties of the breast cancer patients.

Endogenous Q levels, superoxide dismutase, MnSOD, catalase and glutathione

Discussion

To our knowledge, this is the first study of mitochondrial Q concentrations in human breast carcinoma tissues.

We have observed that Q levels in tumor tissues of the breast were lower than corresponding noncancerous tissues. This could reflect consumption of Q against peroxidative damage in tumor tissues. Previous in vivo and in vitro studies have reported that the reduced form of Q, QH2, is an important antioxidant for unsaturated lipids of mitochondrial membranes against free radical damage.

Acknowledgements

We thank Osmangazi University Research Foundation for supporting our study.

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ClinicalCoenzyme Q10 concentrations and antioxidant status in tissues of breast cancer patients

Abstract

Introduction

Section snippets

Methods

Results

Discussion

Acknowledgements

Mut Res

Clin Biochem

Biochim Biophys Acta

Anal Biochem

Biochem Biophy Res Com

Mutat Res

Toxicol Lett

Ann Oncol

Oxy-radical metabolism and control of tumour growth

Xenobiotica

Reactive oxygen species in living systemssource, biochemistry, and role in human disease

Am J Med

Role of free radicals and catalytic metal ions in human diseasean overview

Methods Enzymol

Oxidative mechanism in carcinogenesis

Br Med Bull

Determination of ubiquinones

Methods Enzymol

An analysis of the role of coenzyme Q in free radical generation and as an antioxidant

Biochem Cell Biol

Assay of superoxide dismutase activity in tumor tissue

Methods Enzymol

Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase

J Lab Clin Med

Isolation of mitochondria

J Biol Chem

Studies on reduced and oxidized ubiquinones. I. Simultaneous determination of reduced and oxidized ubiquinones in tissues and mitochondria by HPLC

Chem Pharm Bull

Clinical
Coenzyme Q10 concentrations and antioxidant status in tissues of breast cancer patients