p-CA is a naturally occurring phenolic acid present in most plants and in all commonly consumed vegetables and fruits. Here we demonstrated the anti-cancer effect of the food borne phytochemical p-CA both in vitro and in vivo models of colon cancer using growth rate and tumor incidence as endpoints. Glucose regulated protein (GRP78) induction and UPR activation plays a key role in oncogenic progression, therefore increased dependence of cancer cells on these UPR signaling pathways for survival can be exploited for anti-cancer research. Hence we investigated the effect of p-CA on Grp78 a molecular chaperone often upregulated in colon cancer and its impact on unfolded protein response (UPR). Administration of the procarcinogen 1,2- dimethylhydrazine (DMH) causes Grp78 upregulation and tumor adaptation via UPR activation. The adaptive activity of UPR activates antiapoptotic NF-κB that results in upregulation of the markers of inflammation and angiogenesis. Supplementation of p-CA downregulated Grp78 and activated UPR mediated apoptosis both in in vitro and in vivo models of colon cancer. Further we observed that p-CA significantly reduced inflammation by decreasing the expression of cytokines COX-2, IL-6, TNF-α and PGE2 as analyzed by q-PCR and also reduced the expression of p-p65 and p-IκBα as analyzed by western blot. Further mechanistic insights revealed that p-CA inhibits Grp78 upregulation in cancer cells through activation of PERK-eIF2α-ATF-4-CHOP pathway that culminates in apoptosis inducing effect of p-CA.

p -CA是天然存在的酚酸，存在于大多数植物以及所有常用的蔬菜和水果中。在这里，我们以生长速率和肿瘤发生率为终点，证明了食源性植物化学p -CA在结肠癌的体外和体内模型中的抗癌作用。葡萄糖调节蛋白（GRP78）的诱导和UPR激活在致癌过程中起着关键作用，因此癌细胞对这些UPR信号通路生存的依赖性增加可以用于抗癌研究。因此，我们研究了p的影响-CA在Grp78上是一种分子伴侣蛋白，通常在结肠癌中上调，并且对未折叠的蛋白质反应（UPR）产生影响。施用致癌物1,2-二甲基肼（DMH）会导致Urp激活引起Grp78上调和肿瘤适应。UPR的适应性活性激活抗凋亡的NF-κB，从而导致炎症和血管生成标记物的上调。在结肠癌的体外和体内模型中，p- CA的补充下调了Grp78并激活了UPR介导的细胞凋亡。进一步我们观察到p如通过q-PCR分析，-CA通过降低细胞因子COX-2，IL-6，TNF-α和PGE2的表达来显着减轻炎症，并且通过Western blot分析，还降低p-p65和p-IκBα的表达。进一步的机理研究表明，p -CA通过激活PERK-eIF2α-ATF-4-CHOP途径抑制癌细胞中Grp78的上调，最终导致p -CA的凋亡诱导作用。