Phytochemicals targeting endoplasmic reticulum stress to inhibit cancer cell proliferation

Cancer is marked by uncontrolled cell proliferation avoiding the programmed cell death. Rapid cell division demands increased protein synthesis, overloading endoplasmic reticulum (ER) machinery with enhanced folding, packaging and transportation of proteins causing ER stress. Unfolded protein response (UPR), the adaptive pathway activated by the cell in response to this stress, promotes survival of the cancer cells and hence tumorigenesis. The duration and severity of stress determine the fate of the cell, that is, whether the cell will survive and follow adaptive response or it will lead to apoptosis. Targeting the ER chaperones, UPR machinery and elements that assist in protein folding in the ER lumen might provide a significant therapeutic target against cancer. Phytochemicals can modulate various cellular functions and have been promising agents against cancer. The aim of this chapter is to summarize the possible impact of various phytochemicals like carnosic acid, diallyl sulphur compounds, gambogic acid, galangin, pachymic acid, pomegranate fruit extract, proanthocyanidins and resveratrol, Saccharina japonica n-hexane fraction, 6-shogaol and sulphureuin B, which has the ability to alter ER stress. The anti-proliferative mechanisms of these phytochemicals and their impact on ER stress and cancer progression have also been discussed.