Carotenoids enhance gap junctional communication and inhibit lipid peroxidation in C3H/10T1/2 cells: relationship to their cancer chemopreventive action

Abstract

We have previously demonstrated that diverse carotenoids inhibit chemically induced neoplastic transformation in 10T1/2 cells. To address their mechanism of action, the effects of six diverse carotenoids, with or without provitamin A activity, on gap junctional communication and lipid peroxidation have been investigated. β-Carotene, canthax-anthin, lutein, lycopene and α-carotene increased gap junctional intercellular communication in a dose-dependent manner in the above order of potency, whereas m-bixin was inactive at concentrations up to 10⁻⁵ M. α-Tocopherol, a potent chain-breaking antioxidant, caused a marginal enhancement of junctional communication. The enhancement of junctional communication by diverse carotenoids showed a strong statistical correlation with their previously determined ability to inhibit methylcholanthrene-induced neoplastic transformation (r = −0.75). All carotenoids tested inhibited lipid peroxidation, but with differing potencies. α-Tocopherol was the most active inhibitor followed by m-bixin. The capacity of carotenoids or α-tocopherol to inhibit lipid peroxidation was neither consistent with their ability to inhibit neoplastic transformation (r = 0.30) nor to increase junctional communication (r = 0.12). Since junctional communication appears to play an important role in cell growth control and carcinogenesis, we propose that in this system carotenoid-enhanced intercellular communication provides a mechanistic basis for the cancer chemopreventive action of carotenoids. These data also imply that carotenoids function in a manner analogous to retinoids in the 10T1/2 assay system. Interestingly this activity appears independent of their provitamin A status.