Carotenoids enhance gap junctional communication and inhibit lipid peroxidation in C3H/10T1/2 cells: relationship to their cancer chemopreventive action.
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. beta-Carotene, canthaxanthin, lutein, lycopene and alpha-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. alpha-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. alpha-Tocopherol was the most active inhibitor followed by m-bixin. The capacity of carotenoids or alpha-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.
Cancer Research Center of Hawaii, University of Hawaii, Honolulu 96813.
L X
LX
Zhang
R V
RV
Cooney
J S
JS
Bertram
D000818:Animals; D016644:Canthaxanthin / Q000494:pharmacology; D002338:Carotenoids / Q000494:pharmacology*; D002450:Cell Communication / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects*; D014975:Lutein / Q000494:pharmacology; D000077276:Lycopene; D051379:Mice; D014810:Vitamin E / Q000494:pharmacology; D019207:beta Carotene
D019207:beta Carotene; D014810:Vitamin E; D002338:Carotenoids; C041635:alpha-carotene; D016644:Canthaxanthin; C004588:bixin; D000077276:Lycopene; D014975:Lutein