TABLE 2.

Current evidence on anticancer effects of CHE

Cancer type	Cell line	Duration/dosage	Mechanism	Reference
Lung cancer	NCI-H1299 and A549 cells	10, 15, and 20 μM	Cell viability↓, cell death and apoptosis↑, LC3-I↓, LC3-II↑, cle-PARP↑, and cle-caspase-3↑	Tang et al. (2017)
	NSCLC cell lines (H1299, H460, A549, and cisplatin-resistant A549)	10 µM	Cell apoptosis↑, PKC-α mRNA, and protein↓	Gao et al. (2007)
	SK-LU-1 and human lung cancer stem cells (HLCSCs)	1.5, 3, 6.25, 12.5, 25, and 50 μg/ml	Cell migration and invasion↓, β-catenin↓, ROS↑, MYC↓, SOX2↓, and HLCS activity↓	Heng and Cheah, (2020)
	HCC827	0, 5, 10, 15, 20, 30, and 40 μM	ROS↑, PKC-ϵ↓, caspase-3↓, cell apoptosis↑, cell viability↓, and cell proliferation↓	Wang et al. (2021)
Liver cancer	SMMC-7721 cell	1.25, 2.5, 5, and 10 μg/ml	Cell proliferation↓, cell S-phase arrest↑, Bax↑, Bcl-xl↓, cell apoptosis↑, cyt-c↑, cle-caspase-3↑, and cle-PARP↑	Zhang et al. (2011)
	HCC	1.25, 2.5, and 5 μM	Cell proliferation↓, cell apoptosis↑, p-FAK↓, MMP-2/9↓, and cell metastasis and invasion↓	Zhu et al. (2018)
	HepG2	0.01, 0.1, and 1 μM	CYP1A1↓ and dioxin-induced 7-ethyxoresorufin-O-deethylase (EROD) activity↓	Zdarilová et al. (2006)
Gastric cancer	BGC-823 cells		Δψm↓, cyt-c↑, cle-caspase-3↑, cle-PARP↑, Bcl-xl↓, Bcl-2↓, and cell apoptosis↑	Zhang et al. (2012)
	AGS cells	1 μM, 10 μM, and 100 nM	Cell growth↓, Cells arrested at the G0/G1 phase↑, p53↑, p21(waf/cip1) ↑, c-Myc↓, bax ↑, and cell apoptosis↑	Zhu et al. (1999)
Breast cancer	MDA-MB-231, BT-549, HCC 1937, and MDA-MB-468	5 μM	Cell proliferation↓, cell cycle arrest↑, cell apoptosis↑, and chemotherapy activity↑	Lin et al. (2017)
	MCF-7 and MDA-MB-231	7.5 and10 μM	Cell viability↓, H2O2↑, ROS↑, p-H2AX↑, PARP cleavage↑, and cell apoptosis↑	Matkar et al. (2008); Xie et al. (2015)
	MCF-7 and MCF-7Taxol		PKCa↓, MDR1 gene↓, and P-glycoprotein (P-gp) ↓	Cao et al. (2011)
	GI-101A	50 μM	Cell growth↓ and PKC activity↑,	Fernandez et al. (2000)
	MCF-7	10−8 Μ	Cell proliferation↓ and calcium-dependent PKCs↑	Mueller et al. (1997)
Renal cancer	HEK-293 and SW-839 cells	5 and 10 μM	Cell growth↓, p-ERK↓, p-Akt↓, p53↑, Bcl-2-associated X protein↑, Bcl-2↓, caspase-3↓, PARP↓, and tumor growth↓	Chen et al. (2016)
	Caki and 786-O	6, 9, and 12 μM	Cell viability↓, G2/M cell cycle arrest↑, ROS-dependent ER stress↑, p-STAT3↓, and cell apoptosis↑	He et al. (2019)
Prostate cancer	LNCaP and DU145 cells	0.1, 0.5, 1, 5, and 10 μmol/L	Cell proliferation↓, p21Waf1/Cip1 ↑, p27Kip1↑, p16Ink4↓, retinoblastoma protein↓, and cell apoptosis↑	Malíková et al. (2006)
	PC-3 cells	10 μM	Bcl-2↓, cle-PARP↑, H2O2↑, ROS↑, ER stress↑, p-eIF2α↑, and ATF4↑	Wu et al. (2018)
	DU145 and PC-3 cells	5 and 10 μM	Cell proliferation↓, cell migration and invasion↓, MMP-2↓, MMP-9↓, uPA↓, TIMP-1↑, and TIMP-2↑, PAI-1↑, PAI-2↑, NF-κB↓, AP-1↓, p-p65↓, c-Fos↓, and c-Jun ↓	Yang et al. (2020)
Cervical cancer	HeLa cells	0, 2, 4, and 6 μM,	BAD↑, BAX↑, BAK↑, BCL-2↓, MCL-1↓, cell apoptosis↑, cell proliferation↓, p-PI3Ks↓, AKT↓, mTOR↓, and PKCα↓,	Yang et al. (2020)
Uveal melanoma	OCM-1	8 μg/ml	DNA degradation↑, cell apoptosis↑, and necrotic cell death↑	Kemény-Beke et al. (2006)
Melanoma	A-375, SK-MEL-2, and A-375-p53DD	0.1, 0.5, 1, 1.5, 2, and 3 mg/ml	Cell proliferation↓, cell apoptosis↑, Bcl-xL↓, Mcl-1↓, XIAP↓, caspase-3↓, and PARP↓	Hammerová et al. (2011).
	A375, G-361, SK-MEL-3		Cell viability↑ and cytotoxic activity↑	(Tomasz et al., 2021)
Dalton’s lymphoma	DL cells	10 μg/ml	Cell vitality and proliferation↓, cell apoptosis↑, HSF1↓, and hsp70↓	Kumar et al. (2013)
	DL cells	1–30μM	PKC↓,cyt-c↑,Apaf-1↑,caspase-9↑,caspase-3↑, HSF1 phosphorylation↓, and cell apoptosis↑	Kumar and Acharya, (2014)
	DL-bearing BALB/c (H2d) mice	2.5 mg/kg	Survival duration↑, cytotoxic function↑, and recovery immunosuppression↑	Kumar et al. (2015a)
	DL cells	10 μM	Total-p53/p-p53(ser-15) ↑, cyt-c↑, cle-caspase-9↑, cle-caspase-3↑, and degradation of DNA↑	Kumar et al. (2015b)
Leukemia	HL-60 cells	0.5 μM	Cell differentiation↓	Zheng et al. (2005)
	HL-60 cells	0, 1, 1.5, 2, and 5 μM	Cell cytotoxicity↑, cell viability↓, cell cycle arrest in G1 phase↑, cell cycle distribution↑, cell apoptosis and necrosis↑, cle-caspase-9↑, and cle-caspase-3↑	Vrba et al. (2008)
	KG1a	1, 2, 3, 4, and 5 mol/L	TRAIL-induced apoptosis↑, cle-caspase-8↑, and FLIP↓	Platzbecker et al. (2003)
	CEM T-leukemia human cells	8 μg/ml	EMC cells↑, cell apoptosis↑, fragmentation of DNA↑, and enzyme PARP-1↑	Kaminskyy et al. (2008)
	Mouse lymphocytic leukemia cells, L1210	0.5–8 mg/ml	Cell cytotoxicity↑, plasma membrane integrity↓, DNA damage↑, and cell apoptosis↑	Kaminskyy et al. (2008)
Squamous cell carcinoma	SQ-20B MCF7 breast (wt p53; Ref. 38) and MCF7ADR breast (resistant to adriamycin),	10 μm; 2.5 and 5 mg/kg	Cell apoptosis↑, tumor growth↓, and weight loss↓	Chmura et al. (2000)
	UM-SCC, 8029NA, and 8029DDP	10 μM	Cisplatin IC50 values↓ and cisplatin sensitivity ↑	Hoffmann et al. (2002)