Yeast extract inhibits the proliferation of renal cell carcinoma cells via regulation of iron metabolism

Abstract

The microbiome has recently attracted research interest in a variety of subjects, including cancer. In the present study, it was determined that reinforced clostridium media (RCM) for microbiome culture, exerts antitumor effects on renal cell carcinoma cells when compared to the microbiome 'X'. The antitumor effects of RCM were investigated for all ingredients of RCM, and the results revealed that yeast extract could be a candidate for the ingredient driving this phenomenon. Further experiments including MTT assay, cell counting, cell death analysis, cell cycle analysis and western blotting were conducted with yeast extract on renal cell carcinoma cells (Caki‑1 and Caki‑2) and normal human proximal tubular cells (HK‑2). As a result, yeast extract exhibited dose‑dependent antitumor effects on Caki‑1 and Caki‑2, but only slight effects on HK‑2. In addition, yeast extract only exhibited slight effects on necrosis, autophagy, or apoptosis of Caki‑1 and Caki‑2. Yeast extract produced cell cycle arrest with an increased G0/G1 fraction and a decreased S fraction, and this was considered to be related to the decreased cyclin D1. Although yeast extract treatment increased anti‑oxidant activities, the antitumor effects of yeast extract were also related to iron metabolism, based on the decreased transferrin receptor and increased ferritin. In addition, decreased GPX4 may be related to iron‑dependent cell death, particularly in Caki‑2. These results revealed that yeast extract may inhibit proliferation of renal cell carcinoma cells by regulating iron metabolism. Since an increased iron requirement is a classic phenomenon of cancer cells, yeast extract may be a candidate for adjuvant treatment of renal cell carcinoma.