27‐hydroxycholesterol decreases cell proliferation in colon cancer cells

Abstract

In the United States, Colorectal Cancer is the third most diagnosed cancer, affecting 1 out of approximately 22 people in their lifetime. A major molecule involved in cancer progression is the AKT signaling pathway, which regulates cell cycle progression, protein synthesis, and cellular survival. Several cholesterol metabolites, including 27‐hydroxycholesterol (27‐OHC) have been shown to be involved in breast and prostate cancers. However, the role of 27‐OHC in colon cancer has yet to be determined. The goal of our study is to investigate the potential role of 27‐OHC in colon cancer progression. To study the effects of 27‐OHC, SW620 and Caco2 colon cancer cells were treated with 0.5 μM to 300 μM of 27‐OHC for 24 hours and MTT proliferation assay, LDH cytotoxicity, TUNEL assay, and western blotting was performed. Additionally, cellular migration was measured with a scratch assay. We found a significant decrease in cellular proliferation at supraphysiological concentrations of 27‐OHC (10 μM to 300 μM) with no significant cellular cytotoxicity or apoptotic cell death. Western blotting showed a significant decrease in p‐AKT expression with 10 μM of 27‐OHC in Caco2 cells. In both cell lines there was a significant increase in cellular migration. This data demonstrates that 27‐OHC increases cellular migration through a loss of cellular proliferation. The decrease in cellular proliferation is dependent on p‐AKT in Caco2 cells and an AKT‐independent pathway in SW620 cells, suggesting that 27‐OHC has differential effects on different colon cancer cells.Support or Funding InformationR01AG0145264 awarded to OGThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.