Carotenoids enhance gap junctional communication and inhibit lipid peroxidation in C3H/10T1/2 cells: relationship to their cancer chemopreventive action.
Carotenoids enhance gap junctional communication and inhibit lipid peroxidation in C3H/10T1/2 cells: relationship to their cancer chemopreventive action.
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DOI：
10.1093/carcin/12.11.2109
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发表时间：
1991-11
期刊：
影响因子：
4.7
通讯作者：
Li-Xin Zhang;R. Cooney;J. Bertram
中科院分区：
文献类型：
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作者：
Li-Xin Zhang;R. Cooney;J. Bertram
我们之前已经证明，多种类胡萝卜素可抑制 10T1/2 细胞中化学诱导的肿瘤转化。为了阐明其作用机制，我们研究了六种不同的类胡萝卜素（无论是否具有维生素原 A 活性）对间隙连接通讯和脂质过氧化的影响。 β-胡萝卜素、角黄素、叶黄素、番茄红素和 α-胡萝卜素以上述效力顺序以剂量依赖性方式增加间隙连接细胞间通讯，而 m-bixin 在浓度高达 10(-5) M 时无活性。 α-生育酚是一种有效的链断裂抗氧化剂，引起连接通讯的边缘增强。不同类胡萝卜素对连接通讯的增强与先前确定的抑制甲基胆蒽诱导的肿瘤转化的能力表现出很强的统计相关性（r = -0.75）。所有测试的类胡萝卜素都能抑制脂质过氧化，但效力不同。 α-生育酚是最活跃的抑制剂，其次是 m-红木素。类胡萝卜素或α-生育酚抑制脂质过氧化的能力与其抑制肿瘤转化（r = 0.30）或增加连接通讯（r = 0.12）的能力不一致。由于连接通讯似乎在细胞生长控制和癌发生中发挥重要作用，我们提出在该系统中类胡萝卜素增强的细胞间通讯为类胡萝卜素的癌症化学预防作用提供了机制基础。这些数据还表明，类胡萝卜素在 10T1/2 测定系统中的作用方式与类维生素A 类似。有趣的是，这种活性似乎与它们的维生素原 A 状态无关。
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.