ANTICANCER MECHANISMS OF LYCOPENE ACTION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 本研究的长期目标是在细胞水平上研究番茄红素的抗癌特性。我们的第一个假设是，番茄红素的抗癌特性之一是由于它能够抑制癌细胞的增殖。我们的第二个假设是，番茄红素的抗癌作用之一是由于它能够增加或更新缝隙连接连接蛋白(CX)的蛋白表达。因此，番茄红素维持或创造细胞间的缝隙连接通讯，可以控制肿瘤细胞从周围正常细胞的增殖。我们的第三个假设是，细胞中有额外的受体和配体可以与番茄红素结合，这可能是通过计算化学来确定的。 第一个假设的具体目标1：我们将确定番茄红素的抗癌特性是否包括减少癌细胞系中细胞增殖的能力。第二个假设的特定目标2：我们将确定番茄红素是否以剂量依赖的方式影响培养的癌细胞和非恶性细胞中缝隙连接蛋白和缝隙连接通讯(GJC)的mRNA和蛋白表达。我们将确定番茄红素治疗是否恢复了缝隙连接功能，并将其在癌细胞中的表达与非恶性细胞中的功能进行比较。第三个假设的具体目标3：我们将利用计算化学来研究番茄红素与癌症相关靶点的潜在结合。这将有助于确定哪些受体可能与番茄红素结合。 流行病学研究表明，番茄红素与降低癌症风险有关。番茄红素作为一种膳食补充剂进行了推广和销售，声称其具有抗癌和其他健康益处。番茄红素的有效性和安全性还没有得到具体的评估，也没有确定番茄红素的作用机制。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The long-term goal of this study is to investigate the anticarcinogenic properties of lycopene at the cellular level. Our first hypothesis is that one of lycopenes anticarcinogenic properties is due to its ability to suppress the proliferation of cancer cells. Our second hypothesis is that one of lycopenes anticarcinogenic properties is due to its ability to increase or renew gap junctional connexin (Cx) protein expression. Therefore, lycopene maintains or creates gap junctional communication from cell to cell, which can control proliferation of neoplastic cells from surrounding normal cells. Our third hypothesis is that there are additional receptors and ligands in cells that can bind lycopene, which may be determined with computational chemistry. Specific Aim 1 for the first hypothesis: we will determine if the anticarcinogenic properties of lycopene include the ability to reduce cell proliferation in the cancer cell lines. Specific Aim 2 for the second hypothesis: we will determine if lycopene, in a dose-dependent fashion, affects the mRNA and protein expression of gap junctional connexins and gap junctional communication (GJC) in cultured cancer cells and nonmalignant cells. We will determine if lycopene treatment is restoring the gap junction function and expression in cancer cells compare the function in nonmalignant cells. Specific Aim 3 for the third hypothesis: we will investigate the potential binding of lycopene to cancer-related targets by using computational chemistry. This will help to determine what receptors may be binding to the lycopene. Epidemiological studies have shown that lycopene is associated with a reduced risk of cancer. Lycopene has been promoted and sold as a dietary supplement with claims about its anticancer and other health benefits. The efficacy and safety of lycopene has not been specifically evaluated nor has the mechanism of lycopene action been determined.