Anti-Cancer Natural Products and Their Bioactive Compounds Inducing ER Stress-Mediated Apoptosis: A Review

Abstract

Cancer is the second biggest cause of death worldwide. Despite a number of studies being conducted, the effective mechanism for treating cancer has not yet been fully understood. The tumor-microenvironment such as hypoxia, low nutrients could disturb function of endoplasmic reticulum (ER) to maintain cellular homeostasis, ultimately leading to the accumulation of unfolded proteins in ER, so-called ER stress. The ER stress has a close relation with cancer. ER stress initiates unfolded protein response (UPR) to re-establish ER homeostasis as an adaptive pathway in cancer. However, persistent ER stress triggers the apoptotic pathway. Therefore, blocking the adaptive pathway of ER stress or facilitating the apoptotic pathway could be an anti-cancer strategy. Recently, natural products and their derivatives have been reported to have anti-cancer effects via ER stress. Here, we address mechanisms of ER stress-mediated apoptosis and highlight strategies for cancer therapy by utilizing ER stress. Furthermore, we summarize anti-cancer activity of the natural products via ER stress in six major types of cancers globally (lung, breast, colorectal, gastric, prostate and liver cancer). This review deepens the understanding of ER stress mechanisms in major cancers as well as the suppressive impact of natural products against cancers via ER stress.

Endoplasmic reticulum stress induces apoptosis of arginine vasopressin neurons in central diabetes insipidus via PI3K/Akt pathway

“…Here, in our PEL‐induced CDI model, we demonstrated that in secretory AVP neurons, ER stress may also initiate apoptosis, in agreement with evidence found in other issues. ER stress was reported to be regulated by three canonical signaling pathways: PERK‐eIF2α‐ATF4‐CHOP, IRE1‐XBP1, and ATF6‐ERAD, in various issues . Further, several studies have reported that the PERK‐eIF2α‐ATF4‐CHOP signaling pathway plays an essential role in ER stress‐induced apoptosis, especially in neuronal issues including spinal cord injury, subarachnoid hemorrhage injury, and cerebral ischemia injury .…”

“…ER stress was reported to be regulated by three canonical signaling pathways: PERK-eIF2α-ATF4-CHOP, IRE1-XBP1, and ATF6-ERAD, in various issues. 34 Further, several studies have reported that the PERK-eIF2α-ATF4-CHOP signaling pathway plays an essential role in ER stress-induced apoptosis, especially in neuronal issues including spinal cord injury, subarachnoid hemorrhage injury, and cerebral ischemia injury. 35,36 In the present study, our data indicated consistent involvement of PERK-eIF2α-ATF4-CHOP in ER stress-induced apoptosis in CDI generated by PEL surgery.…”

Paeoniflorin: a monoterpene glycoside from plants of Paeoniaceae family with diverse anticancer activities

“…Thus, finding more candidate drugs for tumour/cancer treatment are of importance. It is reported that half of the current used drugs are derived from the natural agents, and natural components from plants are potential resource for finding effective candidate drugs with low toxicity, and increasing antitumour/cancer researches have suggested that natural compounds are feasible way for finding new antitumour/cancer candidate drugs in the future …”

“…It is reported that half of the current used drugs are derived from the natural agents, and natural components from plants are potential resource for finding effective candidate drugs with low toxicity, [95] and increasing antitumour/cancer researches have suggested that natural compounds are feasible way for finding new antitumour/cancer candidate drugs in the future. [96,97] Paeonia lactiflora, an important TCM, has a long history to widely use in the management of various tumours and inflammatory diseases in China. Modern studies have found that peony and its prescription have good pharmacological effects in the treatment of breast cancer, rheumatoid arthritis, ulcerative colitis and other diseases.…”

Manganese activates autophagy to alleviate endoplasmic reticulum stress–induced apoptosis via PERK pathway

“…4 ER stress-mediated cell apoptosis signalling is activated if the UPR fails to correct misfolded proteins in the ER. 6 However, the mechanisms of ER stress-mediated cell apoptosis remain obscure, and there is far too little distinction regarding which specific effectors of death dominate in specific cellular environment. Furthermore, increasing researches have suggested a role of ER stress-mediated apoptosis in the physiopathology of manganism.…”