The Role of the ER-Induced UPR Pathway and the Efficacy of Its Inhibitors and Inducers in the Inhibition of Tumor Progression

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]