Abstract
Breast cancer is the leading cause of death among women worldwide. Chemoprevention and chemotherapy play beneficial roles in reducing the incidence and mortality of cancer. Epidemiological and experimental studies showed that naturally-occurring antioxidants present in the diet may act as anticancer agents. Identifying the abnormalities of cellular energy metabolism facilitates early detection and management of breast cancer. The present study evaluated the effect of tangeretin on cellular metabolic energy fluxes in 7,12-dimethylbenz(a) anthracene (DMBA)-induced proliferative breast cancer. The results showed that the activities of glycolytic enzymes significantly increased in mammary tissues of DMBA-induced breast cancer bearing rats. The gluconeogenic tricarboxylic acid (TCA) cycle and respiratory chain enzyme activities significantly decreased in breast cancer-bearing rats. In addition, proliferating cell nuclear antigen (PCNA) was highly expressed in breast cancer tissues. However, the activities of glycolytic enzymes were significantly normalized in the tangeretin pre- and post-treated rats and the TCA cycle and respiratory chain enzyme activities were significantly increased in tangeretin treated rats. Furthermore, tangeretin down-regulated PCNA expression on breast cancer-bearing rats. Our study demonstrates that tangeretin specifically regulates cellular metabolic energy fluxes in DMBA-induced breast cancer-bearing rats.
Highlights
Breast cancer is the most common malignancy and the leading cause of death among women worldwide
We evaluated the effect of tangeretin on cellular metabolic energy fluxes in 7,12-d imethylbenz(a) anthracene (DMBA)-induced proliferative breast cancer
Tangeretin treatment for 30 days before the administration of dimethylbenz(a) anthracene (DMBA) in Group III rats and post-treatment with tangeretin in breast cancer-bearing Group IV rats significantly reduced the activities of hexokinase, phosphoglucoisomerase, and aldolase compared with tumor-bearing rats (Group II)
Summary
Breast cancer is the most common malignancy and the leading cause of death among women worldwide. Metabolic energy modulation by tangeretin in breast cancer can generate 2 molecules of lactic acid and 2 molecules of ATP through anaerobic respiration under hypoxic conditions. Warburg found that unlike normal cells, cancer cells generate energy through rapid glycolytic activity even in ample oxygen with the concomitant production of a large amount of lactic acid molecules. Oxidative phosphorylation is inhibited by the production of large amounts of lactic acid This metabolic phenomenon is often called Warburg effect or aerobic glycolysis. Pyruvate kinase forms a complex with other enzymes involved glycolysis and causes glucose to be degraded into pyruvate It is further transformed into lactic acid, and produces an ample amount of energy molecules. We evaluated the effect of tangeretin on cellular metabolic energy fluxes in 7,12-d imethylbenz(a) anthracene (DMBA)-induced proliferative breast cancer
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