Putative tumor suppressor cytoglobin promotes aryl hydrocarbon receptor ligand –mediated triple negative breast cancer cell death

Aryl hydrocarbon receptor ligand 5F 203 induces the expression of putative tumor suppressor cytoglobin (CYGB) and promotes anticancer activity and apoptosis in vivo and in vitro. CYGB promotes 5F 203 –mediated cell death, caspase‐3/‐7 activation, proapoptotic gene expression, lysosomal membrane permeabilization (LMP), and cathepsin B release in triple negative breast cancer (TNBC) cells. These findings suggest that AhR ligands such as 5F 203 upregulate CYGB to confer TNBC cell death. AbstractNearly 40 000 women die annually from breast cancer in the United States. Clinically available targeted breast cancer therapy is largely ineffective in triple negative breast cancer (TNBC), characterized by tumors that lack expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her2). TNBC is associated with a poor prognosis. Previous reports show that aryl hydrocarbon receptor (AhR) partial agonist 2 ‐(4‐amino‐3‐methylphenyl)‐5‐fluorobenzothiazole (5F 203) selectively inhibits the growth of breast cancer cells, including those of the TNBC subtype. We previously demonstrated that 5F 203 induced the expression of putative tumor suppressor gene cytoglobin (CYGB) in breast cancer cells. In the current study, we determined that 5F 203 induces apoptosis and caspase‐3 activation in MDA‐MB‐468 TNBC cells and in T47D ER+ PR+ Her2− breast cancer cells. We also show that caspases and CYGB promote 5F 203 –mediat...
Source: Journal of Cellular Biochemistry - Category: Biochemistry Authors: Tags: RESEARCH ARTICLE Source Type: research