Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, 608 002, Tamil Nadu, India.
Cell Oncol (Dordr). 2012 Oct;35(5):385-95. doi: 10.1007/s13402-012-0099-z. Epub 2012 Sep 15.
Chlorophyllin, a water soluble semi-synthetic food-grade derivative is reported to exhibit a wide range of beneficial health effects. We investigated the effect of chlorophyllin supplementation on Wnt/β-catenin and vascular endothelial growth factor (VEGF) signaling in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis model.
Hamsters were divided into 4 groups. The right buccal pouches of group 1 and 2 hamsters were painted with 0.5 % DMBA for 14 weeks. Group 2 animals received in addition chlorophyllin (4 mg/kg bw) in the diet. Group 3 animals received chlorophyllin alone and group 4 animals served as control. mRNA and protein expression of components of Wnt, VEGF, and PI3K/Akt signaling pathways were analyzed by RT-PCR and Western blot analysis. Dietary chlorophyllin administration suppressed the development of HBP carcinomas by altering the expression of several components of the Wnt/β-catenin signaling pathway. This was associated with inhibition of angiogenesis as evidenced by decreased expression of the proangiogenic factors HIF-1α, VEGF, and VEGFR2. Chlorophyllin administration also downregulated the expression of histone deacetylases involved in epigenetic regulation of tumor angiogenesis.
Dietary chlorophyllin that abrogates Wnt/β-catenin and VEGF signaling by targeting a multitude of key signaling molecules is an attractive candidate for preventing tumor progression.
叶绿酸，一种水溶性半合成食品级衍生物，据报道具有广泛的有益健康的作用。我们研究了叶绿酸补充剂对 7,12-二甲基苯并[a]蒽（DMBA）诱导的颊囊（HBP）致癌模型中 Wnt/β-连环蛋白和血管内皮生长因子（VEGF）信号的影响。
将仓鼠分为 4 组。第 1 组和第 2 组的右侧颊囊用 0.5%DMBA 涂抹 14 周。第 2 组动物还在饮食中添加叶绿酸（4mg/kg bw）。第 3 组动物单独接受叶绿酸，第 4 组动物作为对照。通过 RT-PCR 和 Western blot 分析分析 Wnt、VEGF 和 PI3K/Akt 信号通路成分的 mRNA 和蛋白表达。饮食中叶绿酸的给药通过改变 Wnt/β-连环蛋白信号通路的几个成分的表达来抑制 HBP 癌的发展。这与血管生成的抑制有关，表现为促血管生成因子 HIF-1α、VEGF 和 VEGFR2 的表达减少。叶绿酸给药还下调了涉及肿瘤血管生成的表观遗传调控的组蛋白去乙酰化酶的表达。
通过靶向多种关键信号分子来阻断 Wnt/β-连环蛋白和 VEGF 信号的饮食叶绿酸是预防肿瘤进展的有吸引力的候选药物。
