Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608 002, Tamil Nadu, India.
Food Chem Toxicol. 2012 Mar;50(3-4):867-76. doi: 10.1016/j.fct.2011.12.019. Epub 2011 Dec 21.
Chlorophyllin, a water-soluble, semi-synthetic derivative of the ubiquitous green pigment chlorophyll is shown to exert potent anticarcinogenic effects. In the present study, we investigated the chemopreventive effects of chlorophyllin on 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis by analyzing the expression of NF-κB family members and markers of intrinsic apoptosis. Dietary administration of chlorophyllin (4 mg/kg bw) suppressed the development of HBP carcinomas by inhibiting the canonical NF-κB signaling pathway by downregulating IKKβ, preventing the phosphorylation of IκB-α, and reducing the expression of nuclear NF-κB. Inactivation of NF-κB signaling by chlorophyllin was associated with the induction of intrinsic apoptosis as evidenced by modulation of Bcl-2 family proteins, enforced nuclear localization of survivin, upregulation of apoptogenic molecules, activation of caspases, and cleavage of PARP. The results of the present study demonstrate that chlorophyllin inhibits the development of DMBA-induced HBP carcinogenesis by targeting NF-κB and the intrinsic apoptotic pathway. Thus, dietary agents such as chlorophyllin that simultaneously target divergent pathways of cell survival and cell death are novel candidates for cancer chemoprevention.
叶绿酸是一种广泛存在的绿色色素叶绿素的水溶性半合成衍生物，被证明具有很强的抗癌作用。在本研究中，我们通过分析 NF-κB 家族成员和内在凋亡标志物的表达，研究了叶绿酸对 7,12-二甲基苯并（a）蒽（DMBA）诱导的颊囊（HBP）癌变的化学预防作用。叶绿酸（4mg/kg bw）的饮食给药通过下调 IKKβ、阻止 IκB-α的磷酸化和减少核 NF-κB 的表达，抑制了经典 NF-κB 信号通路，从而抑制了 HBP 癌的发展。叶绿酸对 NF-κB 信号的失活与内在凋亡的诱导有关，这表现在 Bcl-2 家族蛋白的调节、survivin 的强制核定位、促凋亡分子的上调、半胱天冬酶的激活以及 PARP 的切割。本研究的结果表明，叶绿酸通过靶向 NF-κB 和内在凋亡途径抑制 DMBA 诱导的 HBP 癌变的发展。因此，同时针对细胞存活和细胞死亡的不同途径的膳食剂，如叶绿酸，是癌症化学预防的新候选物。
