Soloxolone methyl induces apoptosis and oxidative/ER stress in breast cancer cells and target cancer stem cell population.

One of the most prevalent malignancies in women and one of the leading causes of cancer-related death is breast cancer. There is a need for new treatment approaches and drugs for breast cancer. Many studies show the high potential of triterpene compounds and their semisynthetic derivatives as anticancer agents due to their ability to induce apoptosis and suppress tumorigenesis. The effects of soloxolone methyl (SM), a semisynthetic derivative of 18-H-glycyrrhetinic acid, on the cytotoxicity and apoptosis of human breast cancer cell line (T-47D) and cancer stem cell (CSCs) population (mammospheres; CD44+/CD24-antigen) derived from breast cancer cells, were examined in this work. The ATP assay was used to determine SM growth-inhibitory effects. Fluorescent staining, caspase-cleaved cytokeratin 18, and flow cytometry analysis were used to determine the mode of the cell death. In addition, cell death was investigated at protein and gene levels by Western Blotting and PCR, respectively. SM resulted in cytotoxicity in a time and dose dependent manner via ROS production and ER stress in T-47D cells in 2 models. The mode of cell death was apoptosis, evidenced by phosphatidylserine exposure, caspase activation, and bax overexpression. In mammospheres as 3D model, SM decreased stem cell properties and induced cell death. Taken together, SM may be a promising agent in the treatment of breast cancer, especially due to its antigrowth activity on CSCs.

Mitochondrial miRNAs (MitomiRs): Their potential roles in breast and other cancers.

Breast cancer is the most common cancer in women worldwide. MicroRNAs (miRNAs) are non-coding RNAs that are involved in the post-transcriptional regulation of gene expression. Although miRNAs mainly act in the cytoplasm, they can be found in the mitochondrial compartment of the cell. These miRNAs called "MitomiR", they can change mitochondrial functions by regulating proteins at the mitochondrial level and cause cancer. In this review, we have aimed to explain miRNA biogenesis, transport pathways to mitochondria, and summarize mitomiRs that have been shown to play an important role in mitochondrial function, especially in the initiation and progression of breast cancer.