incretins and Breast-Neoplasms

Female breast cancer recently surpassed lung cancer and became the most commonly diagnosed cancer worldwide. As per the recent data from WHO, breast cancer accounts for one out of every 8 cancer cases diagnosed among an estimated 2.3 million new cancer cases. Breast cancer is the most prevailing cancer type among women causing the highest number of cancer-related mortality. It has been estimated that in 2020, 68,5000 women died due to this disease. Breast cancers have varying degrees of molecular heterogeneity; therefore, they are divided into various molecular clinical sub types. Recent reports suggest that type 2 diabetes (one of the common chronic diseases worldwide) is linked to the higher incidence, accelerated progression, and aggressiveness of different cancers; especially breast cancer. Breast cancer is hormone-dependent in nature and has a cross-talk with metabolism. A number of antidiabetic therapies are known to exert beneficial effects on various types of cancers, including breast cancer. However, only a few reports are available on the role of incretin-based antidiabetic therapies in cancer as a whole and in breast cancer in particular. The present review sheds light on the potential of incretin based therapies on breast cancer and explores the plausible underlying mechanisms. Additionally, we have also discussed the sub types of breast cancer as well as the intricate relationship between diabetes and breast cancer.

Topics: Breast Neoplasms; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Incretins

Incretin therapies have received much attention because of their tissue-protective effects, which extend beyond those associated with glycemic control. Cancer is a primary cause of death in patients who have diabetes mellitus. We previously reported antiprostate cancer effects of the glucagonlike peptide-1 (GLP-1) receptor (GLP-1R) agonist exendin-4 (Ex-4). Breast cancer is one of the most common cancers in female patients who have type 2 diabetes mellitus and obesity. Thus, we examined whether GLP-1 action could attenuate breast cancer. GLP-1R was expressed in human breast cancer tissue and MCF-7, MDA-MB-231, and KPL-1 cell lines. We found that 0.1 to 10 nM Ex-4 significantly decreased the number of breast cancer cells in a dose-dependent manner. Although Ex-4 did not induce apoptosis, it attenuated breast cancer cell proliferation significantly and dose-dependently. However, the dipeptidyl peptidase-4 inhibitor linagliptin did not affect breast cancer cell proliferation. When MCF-7 cells were transplanted into athymic mice, Ex-4 decreased MCF-7 tumor size in vivo. Ki67 immunohistochemistry revealed that breast cancer cell proliferation was significantly reduced in tumors extracted from Ex-4-treated mice. In MCF-7 cells, Ex-4 significantly inhibited nuclear factor κB (NF-κB ) nuclear translocation and target gene expression. Furthermore, Ex-4 decreased both Akt and IκB phosphorylation. These results suggest that GLP-1 could attenuate breast cancer cell proliferation via activation of GLP-1R and subsequent inhibition of NF-κB activation.

Topics: Adult; Animals; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Exenatide; Female; Gene Expression Regulation, Neoplastic; Glucagon-Like Peptide-1 Receptor; Humans; Incretins; MCF-7 Cells; Mice, Nude; Middle Aged; NF-kappa B; Peptides; Venoms; Xenograft Model Antitumor Assays