Table 2.
UPR-modulating factors inducing ER stress activity in cancer cells.
| Agents | Mechanism | Cancer type/cell lines | References |
|---|---|---|---|
| GSK2606414 and GSK2656157 | p-PERK↓, p-elF2α↓ | Multiple myeloma | [88, 89] |
| STF-083010 | Ire1 inhibitor | Multiple myeloma | [91] |
| Sorafenib tyrosine kinase inhibitor (TKI) | CHOP↑ GADD34↑; p-PERK↑; p-elF2α↑ | L-428, L-1236, and KM-H2 cells | [92] |
| Sal003, inhibitor of phospho-eif2α phosphatase | ATF4; p-elF2α↑ | Glioblastoma cells | [25] |
| Diindolylmethane derivatives | CHOP↑; DR5↑ | Pancreatic cancer cells | [93] |
| Bortezomib proteasome inhibitor | GRP78↑, CHOP↑, JNK↑, p-eIF2α↓ | L3.6pl pancreatic cancer cells | [94] |
| Levistolide A | ROS↑; CHOP↑ | Colorectal cancer cells | [97] |
| Andrographolide | ROS↑; CHOP↑ | Colorectal cancer cells | [99] |
| Tolfenamic acid | eIF2α↑; ATF4↑ | Colorectal cancer cells | [98] |
| Cantharidin | GRP78/BiP ↑, IRE1α ↑, IRE1β ↑, ATF6α ↑, XBP1 ↑ | H460 | [100] |
| Carnosic acid | ROS↑; CHOP↑; ATF4↑ | Renal carcinoma Caki cells | [101] |
| Casticin | CHOP ↑, p-eIF2α ↑, eIF2α ↑, GRP78/BiP ↑ | BGC-823 | [102] |
| Cryptotanshinone | p-eIF2α ↑, GRP94 ↑, GRP78 ↑, CHOP ↑, ROS↑ | MCF7 | [103] |
| Curcumin | CHOP ↑, GRP78/BiP ↑, ROS ↑ | NCI-H460, HT-29, AGS | [104, 105] |
| Flavokawain B | CHOP ↑, ATF4 ↑ | HCT116 | [106] |
| Fucoidan | CHOP ↑, ATF4 ↑, p-eIF2α ↑, GRP78/BiP ↓, p-IRE1 ↓, XBP1 ↓ | MDA-MB-231 HCT116 | [107] |
| Furanodiene | CHOP ↑, BIP ↑ | A549, 95-D | [108] |
| 2-3,4 Dihydroxyphenylethanol | IRE1 ↑, XBP1 ↑, GRP78/BiP ↑, PERK ↑, eIF2α ↑, CHOP ↑ | HT-29 | [109] |
| 7-Dimethoxyflavone | CHOP ↑, GPR78/BiP ↑, ATF4 ↑ | Hep3B | [110] |
| SMIP004 (N-(4-butyl-2-methyl-phenyl) acetamide) | ROS↑ IRE1↑; p-38↑; p-elF2α↑ | Prostate cancer cells | [111] |
| Licochalcone A | ATF6 ↑, eIF2α ↑, IRE1α ↑, CHOP ↑, GRP94 ↑, XBP1 ↑, GRP78/BiP ↑ | HepG2 | [112] |
| Neferine | GRP78/BiP ↑ | Hep3B | [113] |
| Paeonol | GRP78 ↑, CHOP ↑ | HepG2 | [114] |
| Pardaxin | ROS↑; p-PERK↑; p-elF2α↑ | HeLa cells | [115] |
| Parthenolide | ATF4 ↑, p-eIF2a ↑, eIF2α ↑ | A549, Calu-1, H1299, H1792 | [116] |
| Piperine | IRE1α ↑, CHOP ↑, GPR78/BiP ↑ | HT-29 | [117] |
| Polyphenon E | ATF4 ↑, PERK ↑, p-eIF2α ↑, eIF2α ↑, GRP78/BiP ↑, CHOP ↑, XBP1 ↑, ROS ↑ | PC3, PNT1a | [118] |
| Polyphyllin D | CHOP ↑, GRP78/BiP ↑, PDI ↑ | NCI-H460 | [119] |
| Resveratrol | GRP78/BiP ↑, CHOP ↑, XBP1 ↑, eIF2α ↑ | HT29 | [120] |
| Dehydrocostuslactone | p-PERK ↑, GRP78/BiP ↑, IRE1 ↑, CHOP ↑, XBP-1 ↑, ROS ↑ | NCI-H460 A549 | [121] |
| γ-Tocotrienol | CHOP ↑, GRP78/BiP ↑, XBP1 ↑ | MDA-MB-231; MCF-7 | [122] |
| Ω-Hydroxyundec-9-enoic Acid (ω-HUA) | ROS↑; CHOP↑ | Lung cancer cells (H1299, A549, HCC827) | [123] |
| Ampelopsin | ROS↑ GRP78↑; p-PERK↑; p-elF2α↑ | Breast cancer cells (MCF-7; MDA-MB-231) | [124] |
| Ardisianone | GRP78/BiP ↑ | PC3 | [125] |
| Genistein | CHOP ↑, GRP78/BiP ↑ | Hep3B | [126] |
| Guttiferone H | ATF4 ↑, XBP1 ↑, CHOP ↑ | HCT116 | [127] |
| Guggulsterone | ROS↑; p-eIF2α↑; CHOP↑ DR5↑ | Liver cancer cells (Hep3B; HepG2) | [128] |
| Marchantin M | GRP78/BiP, CHOP ↑, XBP1 ↑, p-eIF2α ↑, eIF2α ↑, ATF4 ↑, ATF6 ↑, ERAD ↓ | PC3, DU145, LNCaP | [129] |
| Sarsasapogenin | ROS↑; CHOP↑ | HeLa cells | [130] |
| Saxifragifolin | IRE1α ↑, XBP1 ↑, CHOP ↑, GRP78/BiP ↑, ROS↑ | MDA-MB-231, MCF7 | [131] |
| Prodigiosin | ROS↑; CHOP↑; p-eIF2α↑; PERK↑; GRP78↑; ATF6α↑, IRE1 ↑, eIF2a ↑ | Pancreatic (8898); breast cancer cells (MCF-7 and MDA-MB-231) | [132, 133] |
| Quercetin | GRP78/BiP ↑, ATF4 ↑, IRE1α ↑ ATF6 ↑ | PC3 | [134] |
| Honokiol (HNK) | ROS↑ p-eIF2α↑; GRP78↑ CHOP↑ | Chondrosarcoma (JJ012 and SW1353); gastric (AGS, SCM-1 and MKN-45) cancer cells | [135–139] |
| Brefeldin A (BFA) | ROS↑, IRE1α ↑, PERK ↑, XBP1↑; GRP78↑ CHOP↑ | Ovarian (OVCAR-3); lung (A549); colorectal (colo 205); breast (MDA-MB-231) cancer cells | [140–142] |
| A-tocopheryl succinate | SGC-7901 | GRP78/BiP ↑, CHOP ↑ | [143] |
| Verrucarin A | GRP78/BiP ↑, p-PERK ↑, p-eIF2α ↑, CHOP ↑ | Hep3B, HepG2 | [144] |
| Vitamin E succinate | GRP78/BiP ↑, GRP94 ↓, PERK ↑, ATF4 ↑, ATF6 ↑, XBP1 ↑, CHOP ↑ | SGC-7901 | [145] |
| Ultrafine | p-eIF2α ↑, GRP78/BiP ↑ | SNU-484 | [146] |
| Zerumbone | ATF4 ↑, CHOP ↑, GRP78/BiP ↑, p-PERK ↑, PERK ↑ eIF2α ↑, p-eIF2α ↑ | HCT116-p53null, SW480, PC3 | [68, 147] |