Table 2.

Anti-cancer effects of escin revealed by in vitro or in vivo studies.

Cancer Type	Model System	Anti-Cancer Effects and Mechanisms of Escin by			Ref.
		Inducing Cell Apoptosis	Decreasing Cell Proliferation	Inhibiting Metastasis and Invasion
Bladder cancer	T24, J82, TCCSUP, and RT-4 cell lines	Through death receptor and mitochondria mediated pathways	↓ NF–κB p65, partially affects STAT3 expression		[28]
Breast cancer	MDA-MB-231 cell line			↓ LOXL2, ↓ c-Myc, ↓ GSL1, ↑ASCT2	[29,30]
	Mice and MCF-7 cell line	Yes	Yes	↑ p53, ↓ Bcl-2	[31,32,33,34]
Colon cancer	HT-29 cell line		Cell cycle arrest at G1/S phase mediated by induction of p21WAF1/CIP1		[35]
	LoVo cell line		Yes		[36]
Colorectal cancer	Mice and HCT116, HCT8 cell lines	Through DNA damage	Yes		[37]
	Mice and HCT116, HCT8 cell lines	Through DNA damage ↑ TIGAR ↑ ROS	Yes		[38]
Cholangiocarcinoma	QBC939, MZ-ChA-1 Sk-ChA-1 cell lines	↑ caspase-3, ↓ Bcl-2	Cell cycle arrest at G1 and G2/M phases		[39]
	QBC939 cell line	Sensitised to 5-FU and VCR	↓ P-glycoprotein, ↓ GSK3b/ catenin		[40]
Gastric cancer	AGS cell lines			Through Akt signalling pathway	[41]
Glioblastoma multiforme	Classical and mesenchymal glioblastoma-initiating cells	Through mitochondria-mediated pathway	Yes		[42]
Hepatocellular carcinoma	SMMC-7721 cell line	↑ caspases 3, 8, 9; ↓ Bcl-2 with 5-FU	Cell cycle arrest at G0/G1 with 5-FU		[43]
	HepG2 cell line	↑ PARP, AIF, BAX, and Bcl-2	Cell cycle arrest at G1/S phase		[44]
	HepG2 cell line		↓ Akt/JAK/STAT, ↓ cyclin D1, ↓ Bcl-2, ↓ Bcl-xL, ↓ survivin, ↓ Mcl-1, ↓ VEGF; sensitised to Dx, PTX		[45]
Leukaemia	Jurkat T-cell line	↑ Caspases-3, 8, 9, ↓ PARP, ↓ Bcl-2, ↑ ROS	Yes		[32,46]
	CEM cell line		Yes		[32]
	KBM-5 cell line	TNF-induced apoptosis	↓ TNF ↓ NF–κB	↓ TNF ↓ NF–κB	[47]
Lung cancer	A549 cell line		Through JAK/STAT signalling pathway	↓ iNOS	[48]
	Mice and H460 cell line		↓ ALDH1A1 ↓ p-Akt, ↑ p21	↓ RhoA and Rock	[49]
	A549 cell line	↑ BAX, ↑ caspase-3	Cell cycle arrest at G0/G1phase		[50]
Melanoma	SK-MEL5 and B16F10 cell lines		↓ NF–κB, ↓ IκB	Through ERK1/2 signalling	[51]
Osteosarcoma	Mice and MNNG/HOS, Saos-2, MG-63, U-2OS, HUVEC cell lines	Through ROS/p38 MAPK signalling pathway			[52]
	Mice and MG-63, OS732 cell lines	↑ Caspases-3, 8, 9	↓ PI3K/Akt pathway		[53]
Ovarian cancer	HeyA8, SNU-119, Kuramochi, Ovcar4, and Ovcar5 cell lines			↓ Autophagy-dependent CSC differentiation, ↓ Stromal ECM production driven by HIF1α	[54]
Pancreatic cancer	Mice and BxPC-3, PANC-1 cell lines	↓ NF–κB, ↓ c-Myc, ↓ COX-2, ↓ cyclin D1, ↓ survivin, ↓ Bcl-xL, ↓ Bcl-2, ↑ caspase-3			[55]
	COLO357, MIA-Paca, Panc-1, cell lines	Yes	↓ NF–κB, ↓ cyclin D, sensitised cells to cisplatin		[56]
	BxPC-3, AsPC-1, SW1990 cell lines		↓ NF-κB	↓ IL-8, ↓ VEGF	[57]
Prostate cancer	Mice and CRPC, PC-3, DU-145 cell lines	↑ c-caspase-3, ↑ BAX, ↓ Bcl-2, ↓ cIAP-1, ↓ cIAP-2 ↓ xIAP, ↑ PARP	Cell cycle arrest at G2/M-phase		[58]
Renal cancer	786-O and Caki-1 cell lines	↓ Bcl-2, ↑ ROS	Cell cycle arrest at G2/M arrest		[59]

Abbreviations: Dx—doxorubicin, IL—interleukin, PTX—paclitaxel, VCR—Vincristine, LOXL2—lysyl oxidase-like 2, EMT—epithelial-mesenchymal transition, 5-FU—5-Fluorouracil, CSC—cancer stem cell, GLS1—kidney type glutaminase, ASCT2—alanine-serine-cysteine 2 protein, MAPKs—p38 mitogen-activated protein kinases, NF-κB—Nuclear factor kappa B, ROS—reactive oxygen species, TIGAR—TP53-induced glycolysis and apoptosis regulator, CXCL16—chemokine (C-X-C motif) ligand, iNOS—inducible nitric oxide synthase, ERK1/2—extracellular signal-regulated kinase 1/2, PARP (c)—poly (adenosine diphosphateribose) polymerase, Bcl-2—B-cell lymphoma 2 proteins, BAX—BCL2-associated X, Bcl-xL—X-linked inhibitor of apoptosis protein (xIAP), ALDH—aldehyde dehydrogenase, p-Akt—phospho-Akt, HUVECs—human umbilical vein endothelial cells, VEGF—vascular epidermal growth factor, ECM—extracellular matrix, and HIF1α—Hypoxia-inducible factor 1-alpha.