Chidambara Murthy K N, Kim Jinhee, Vikram Amit, Patil Bhimanagouda S
Vegetable and Fruit Improvement Center, Department of Horticultural Sciences, Texas A&M University, College Station, TX 77845-2119, USA.
Vegetable and Fruit Improvement Center, Department of Horticultural Sciences, Texas A&M University, College Station, TX 77845-2119, USA.
Food Chem. 2012 May 1;132(1):27-34. doi: 10.1016/j.foodchem.2011.10.014. Epub 2011 Oct 13.
A number of studies in the recent years have evaluated the anti-proliferative activity of flavonoids. Although certain studies investigated the structure-activity based on the phenotypic assays, no study has correlated the flavonoids structure with the ability to alter gene/protein expression. Present study was focused to understand the structure-function relationship of citrus flavonoids in terms of their ability to alter the gene expression in the colon adenocarcinoma cells. Eight structurally related flavonoids found in citrus were evaluated for their ability to inhibit colon cancer (SW480) cells, as well as change the expression of apoptosis related genes/proteins. Apigenin and quercetagetin demonstrated most significant inhibition of cell proliferation with 63.6% and 45.7% inhibition of cell growth at 200μM after 48h of incubation, respectively. The cell death was also confirmed by images of fluorescently tagged cells. Furthermore, up-regulation of Bax/Bcl2 protein ratio as well as activation of Caspase3 at 200μM at 48h confirmed the induction of apoptosis by apigenin and quercetagetin. In addition, results suggest that the change in Bax/Bcl2 ratio by apigenin and quercetagetin seems to be due to their ability to alter the expression of bax and bcl2 transcription. Results of the currents study suggest that among the citrus flavonoids, double bond between C2 and C3 and hydroxyl group at C3, C6 are highly decisive for the proliferation inhibition and apoptosis induction ability. Taken together, these results demonstrate that among the major flavonoids of citrus, apigenin and quercetagetin have potent anti-cancer activity through inducing apoptosis in SW480 human colon cancer cells.
近年来，多项研究评估了黄酮类化合物的抗增殖活性。尽管某些研究基于表型分析研究了结构-活性关系，但尚无研究将黄酮类化合物的结构与改变基因/蛋白质表达的能力联系起来。本研究旨在了解柑橘类黄酮在改变结肠腺癌细胞基因表达方面的结构-功能关系。对柑橘中发现的八种结构相关的黄酮类化合物进行了评估，以确定它们抑制结肠癌（SW480）细胞的能力，以及改变凋亡相关基因/蛋白质表达的能力。芹菜素和槲皮黄素对细胞增殖的抑制作用最为显著，在200μM浓度下孵育48小时后，细胞生长抑制率分别为63.6%和45.7%。荧光标记细胞的图像也证实了细胞死亡。此外，在48小时时，200μM浓度下Bax/Bcl2蛋白比值的上调以及Caspase3的激活证实了芹菜素和槲皮黄素诱导细胞凋亡。此外，结果表明，芹菜素和槲皮黄素引起的Bax/Bcl2比值变化似乎是由于它们改变bax和bcl2转录表达的能力。本研究结果表明，在柑橘类黄酮中，C2和C3之间的双键以及C3、C6处的羟基对增殖抑制和凋亡诱导能力具有高度决定性作用。综上所述，这些结果表明，在柑橘的主要黄酮类化合物中，芹菜素和槲皮黄素通过诱导SW480人结肠癌细胞凋亡具有强大的抗癌活性。
