Differences in nonoxidative sulfur metabolism between normal human breast MCF-12A and adenocarcinoma MCF-7 cell lines

Abstract

Recent studies have revealed the role of endogenous hydrogen sulfide (H₂S) in the development of breast cancer. The capacity of cells to generate H₂S and the activity and expression of the main enzymes (cystathionine beta synthase; CBS, cystathionase γ-lyase; CGL, 3-mercaptopyruvate sulfurtransferase; MPST and thiosulfate sulfurtransferase; TST) involved in H₂S metabolism were analyzed using an in vitro model of a non-tumourigenic breast cell line (MCF-12A) and a human breast adenocarcinoma cell line (MCF-7). In both cell lines, MPST, CGL, and TST expression was confirmed at the mRNA (RT-PCR) and the protein (Western Blot) level, while CBS expression was detected only in MCF-7 cells. Elevated levels of GSH, sulfane sulfur and increased CBS and TST activity were presented in the MCF-7 compared to the MCF-12A cells. It appears that cysteine might be mainly a substrate for GSH synthesis in breast adenocarcinoma. Increased capacity of the cells to generate H₂S was shown for MCF-12A compared to MCF-7 cell line. Results suggest an important function of CBS in H₂S metabolism in breast adenocarcinoma. The presented work may contribute to further research on new therapeutic possibilities for breast cancer - one of the most frequently diagnosed types of cancer among women.

Keywords: 3-mercaptopyruvate sulfurtransferase; Breast adenocarcinoma and normal breast cells; Cystathionase γ-lyase; Cystathionine beta synthase; Hydrogen sulfide; Thiosulfate sulfurtransferase.