ER 스트레스 매개 세포자멸사를 유도하는 항암 천연물

2018

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115829/

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

Bioactive compounds from natural products that induce ER-stress-mediated apoptosis in lung cancer.

 

Family                   NameCompound             Duration/Dosage                  MechanismReference

Paris polyphylla	Polyphyllin D		1.8 µM, 8 h	CHOP ↑, GRP78/BiP ↑, PDI ↑
				cleavage of caspase-3,-4,-9,-12 ↑, Bax ↑, Bcl-2 ↓
Saussurea lappa  and Aucklandia lappa	Dehydrocostuslactone		15 μg/mL, 1 h	release of intracellular Ca2+ levels ↑, Δψm ↓, p-PERK ↑, GRP78/BiP ↑, IRE1 ↑, CHOP ↑, XBP-1 ↑
				Cleavage of caspase-4 ↑, JNK ↑, MAPK ↑
				ROS ↑
			15 μg/mL, 1 h	release of intracellular Ca2+ ↑, Δψm ↓,p-PERK ↑, GRP78/BiP ↑, IRE1 ↑, CHOP ↑, XBP1 ↑
				JNK ↑, MAPK ↑, cleavage of caspase-4 ↑
				ROS ↑
	BrefeldinA		1 µM, 36 h	p-PERK ↑, IRE1α ↑, ATF4 ↑, ATF6 ↑, CHOP ↑, GRP78/BiP ↑
				cleavage of PARP ↑, cleavage of caspase-2 ↑, Bid ↑
Oryza officinalis	ω-Hydroxyundec-9-enoic acid		500 µM, 24 h	p-eIF2α ↑, CHOP ↑
				cleavage of caspase-6,-9 ↑, cleavage of PARP ↑
				ROS ↑
Curcuma longa	Curcumin		25 µM, 24 h	release of intracellular Ca2+ ↑, Δψm ↓, CHOP ↑, GRP78/BiP ↑
				Bcl-2 ↓, Bcl-xL ↓, cytochrome c ↑, cleavage of caspase-3,-8,-9 ↑, BAX ↑, BAD ↑
				ROS ↑
Mylabris phalerata  Pallas	Cantharidin		10 µM, 24 h	release of intracellular Ca2+ ↑, Δψm ↓, GRP78/BiP ↑, IRE1α ↑, IRE1β ↑, ATF6α ↑, XBP1 ↑, calpain ↑,
				Bcl-xL ↓, cleavage of caspase-3,-8,-4 ↑ cytochrome c ↑ BAX ↑, AIF ↑, Endo G ↑
				ROS ↑
Curcumae Rhizoma	Furanodiene		80 µM, 24 h	CHOP ↑, BIP ↑
Tanacetum parthenium L.	Parthenolide		20 µM, 24 h	ATF4 ↑, p-eIF2a ↑, eIF2α ↑
				cleavage of caspase-3,-8,-9 ↑, cleavage of PARP ↑
Anacardium occidentale	Anacardic acid		3.0 μg/mL, 18 h	release of intracellular Ca2+ ↑, Δψm ↓, GRP78/BiP ↑, CHOP ↑, IRE1α ↑ ATF6 ↑, p-PERK ↓, p-eIF2α ↓
				cleavage caspase-12 ↑

Glucose-regulated protein 78 (GRP78); binding protein (BiP); protein disulphide isomerase (PDI); protein kinase RNA-like ER kinase (PERK); reactive oxygen species (ROS); inositol-requiring protein 1 (IRE1); ↑ - increasing concentration; ↓ - decreasing concentration; activating transcription factor 4 (ATF4); activating transcription factor 6 (ATF6); B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax); X-ox binding protein 1 (XBP-1); c-Jun-N terminal kinase (JNK); mitochondrial membrane potential (Δψm); C/EBP-homologous protein (CHOP); α-x-box binding protein 1 (XBP1); apoptosis-inducing factor (AIF); and eukaryotic initiation factor 2 (eIf2).