Cellular metabolic energy modulation by tangeretin in 7,12-dimethylbenz(a) anthracene-induced breast cancer

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.

Therapeutic Implications of a Polymethoxylated Flavone, Tangeretin, in the Management of Cancer via Modulation of Different Molecular Pathways

“…However, treated rats with tangeretin exhibited normalization in the level of glycolytic enzymes as well as a significant rise in the activities of the citric acid cycle and respiratory chain enzyme. Moreover, the expression of PCNA was downregulated [ 95 ].…”

Insulin receptor is implicated in triple-negative breast cancer by decreasing cell mobility

“…Triple-negative breast cancer (TNBC) represents approximately 10% to 15% of all breast cancers and is a highly aggressive subtype of tumors that lack estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) gene amplification [ 1 – 2 ] . Although the prognosis of most breast cancer is greatly improved due to earlier detection and application of new treatment approaches, such as target therapy, the prognosis of TNBC remains poor [ 3 – 4 ] . In comparison with other breast cancer subtypes, TNBC has an earlier onset of metastasis.…”