Inhibition of chemically induced neoplastic transformation by carotenoids. Mechanistic studies

In 10T1/2 cells several dietary carotenoids have been shown to be capable of inhibiting carcinogen-induced neoplastic transformation. Their action appears qualitatively similar to the previously documented action of retinoids in this cell system. However, higher concentrations (10-1000-fold) are required. Both types of compound were found to strongly upregulate gap junctional intercellular communication at concentrations which inhibit transformation. Upregulation of gap junctional intercellular communication was caused by the increased expression of connexin 43, a junctional protein. This activity of carotenoids and retinoids is highly correlated with, and has been proposed to be mechanistically linked to, inhibition of transformation in 10T1/2 cells. In this model the gap junction serves as a conduit for growth regulatory signals from normal to initiated cells. These putative signals act to suppress transformation of the initiated cell.