Table 1.

Anticancer activity of Xn in vitro.

Cancer types		Cell lines	Dose or IC50 (μM)	Duration (h)	Finding	Mechanism	Reference
Respiratory system cancers	NSCLC	A549	5–25	48	↓ Cell viability ↓ Proliferation ↑ Apoptosis	↓ ERK1/2 ↓ p90RSK kinases ↓ CREB ↑ p53 and p21 ↓ Cyclin D1 Cycle arrest (G1 phase) ↑ Caspase-3 activity	Slawinska-Brych et al., 2016
		A549	5–30	6, 24	↑ Apoptosis	↓ NADH dehydrogenase ↑ Glycolysis ↑ ROS	Zhang et al., 2015
		A549	14, 28, 42	24, 48, 72	↓ Proliferation ↑ Apoptosis	Cycle arrest (S phase) ↑ Caspase-3, -8, -9	Yong et al., 2015
Lymphatic hematopoietic cancers	Leukemia	Acute lymphoblastic leukemia L1210 and adriamycin-resistant L1210	2.5, 5, 10	48, 96	↓ Cell viability ↑ Apoptosis ↓ Migration ↓ Invasion	↓ FAK, ↓ AKT ↓ NF-κB signaling pathways	Benelli et al., 2012
		Chronic myeloid leukemia KBM-5	50	4	↑ Apoptosis ↓ Invasion	↓ IKK activity ↓ IκBα phosphorylation and degradation ↓ p65 nuclear translocation ↓ NF-κB controlled antiapoptotic genes (Bcl-xL, cIAP-1, cIAP-2, XIAP, survivin, and TRAF-2)	Harikumar et al., 2009
		Bcr-Abl (+) myeloid leukemia cells K562	2.5, 5, 10	24	↓ Cell viability ↑ Apoptosis ↓ Invasion ↓ Adhesion to endothelial cells	↓ Bcr-Abl ↑ p21 ↑ p53 ↓ MMP-2	Monteghirfo et al., 2008; Vakana and Platanias, 2011
Digestive system cancers	Hepatocellular carcinoma	Huh-7, HepG2, Hep3B, and SK-Hep-1	5	96	↓ Cell viability ↓ Colony forming ↓ Confluency ability	↓ Notch1 ↓ HES-1	Kunnimalaiyaan et al., 2015a
		HepG2	10	24	None	None	Plazar et al., 2007
		HA22T/VGH and Hep3B cells	IC50 = 108, 166	24	None	None	Ho et al., 2008
	Cholangiocarcinoma	KKU-M214, KKU-M139	20, 50	24, 48,72	↓ Cell growth	↓ STAT3 activation	Dokduang et al., 2016
	Pancreatic cancer	PANC-1, BxPC-3	5–100	48	↓ Cell viability ↓ Colony formation ↑ Apoptosis	↓ p-STAT3	Jiang et al., 2015
		AsPC-1, PANC-1, L3.6pl, MiaPaCa-2, 512, 651	10	48-96	↓ Proliferation	↓ Notch1 ↓ HES-1 ↓ Survivin	Kunnimalaiyaan et al., 2015b
	Colon cancer	HT-29	0.1–100	48, 72	↓ Cell viability	None	Miranda et al., 1999
		40-16 colon cancer cells	IC50 = 4.1, 3.6, 2.6	24, 48, 72	↓ Proliferation	None	Pan et al., 2005
		HCT-115	IC50 = 10.2	24	↓ Proliferation	↓ ABCB1 ↓ ABCC1, ABCC2, ABCC3	Lee et al., 2007
Genitourinary organ cancers	Breast cancer	MDA-MB-231 and Hs578T	IC50 = 6.7, 4.78	24	↓ Proliferation ↓ Cell invasion	None	Kim et al., 2013
		MDA-MB-231	10, 20	48	↓ Cell viability	↓ Bax ↑ Caspase-3, -9	Yoo et al., 2014
		MCF-7	10	48	↓ Proliferation	↓ ALP isoenzymes	Guerreiro et al., 2007
		Adriamycin-resistant MCF-7 (MCF-7/ADR)	10	24, 48	↓ Cell viability ↑ Apoptosis ↓ Stemness ↑ Chemo-sensitizing ↑ Radio-sensitizing	↑ γ-H2AX ↓ MDR1 ↓ EGFR ↓ STAT3	Kang et al., 2013; Liu M. et al., 2016
	Prostate cancer	Hormone-sensitive (AR+): LNCaP; hormone-refractory (AR-): PC-3 and DU145	20, 40	72	↓ Cell viability ↑ Apoptosis	↓ p-AKT ↓ NF-κB p65 ↓ p-mTOR ↓ Bcl-2 ↓ Survivin	Deeb et al., 2010
		Hormone-refractory (AR-): PC-3	2.5–20	48h	↓ Cell viability ↑ Apoptosis	↓ NF-κB activation	Colgate et al., 2007
		Hormone-refractory (AR-): PC-3 and DU145DU145, PC3	2.5, 5, 10	48, 96	↓ Proliferation ↓ Cell migration ↓ Cell invasion	↓ p-FAK ↓ p-AKT	Vene et al., 2012
	Cervical cancer	Ca Ski	IC50 = 59.96 ± 1.95, 34.01 ± 1.13, 20.08 ± 1.12	24, 48, 72	↓ Proliferation ↑ Apoptosis	↓ XIAP ↑ p53 ↑ Caspase-3, -8, -9 Cycle arrest (S phase)	Yong and Abd Malek, 2015
	Ovarian cancer	A-2780	IC50 = 0.52, 5.2	48, 96	↓ Proliferation	None	Miranda et al., 1999
		SKOV3, OVCAR3	10, 20, 30	96, 144	↓ Proliferation	↓ Notch1 ↑ p21 Cycle arrest (S and G2/M)	Drenzek et al., 2011
Head and neck cancers	Glioblastoma	U87 glioblastoma cells	25	24	↓ Cell viability ↑ Apoptosis	↑ ERK/c-Fos ↑ miR-204-3p ↓ IGFBP2/AKT/Bcl2	Chen et al., 2016
		T98G	20	24, 48	↓ Cell viability ↑ Apoptosis	↑ ROS ↑ p-ERK1/2 ↑ p-p38 ↑ Caspase-3, -9 ↑ PARP cleavage	Festa et al., 2011
	Thyroid cancer	Medullary thyroid cancer cells MTC	10, 20, 30	96	↓ Proliferation ↓ Malignant phenotype	↑ ERK1/2 phosphorylation	Cook et al., 2010
	Laryngeal squamous cell carcinoma	RK33 and RK45	IC50 = 12.3, 22.5	48	↓ Cell viability ↑ Apoptosis	↑ p53 and p21 ↓ Cyclin D1 ↓ ERK1/2 phosphorylation ↑ Caspase-3, -8, -9 Cycle arrest (G1 phase)	Slawinska-Brych et al., 2015
		SCC4	20, 30, 40	48	↓ Proliferation ↑ Apoptosis	↓ Bcl-2 ↓ Mcl-1 ↑ PARP ↑ p53 ↑ AIF	Li et al., 2016
Other cancers	Melanoma	B16	0.5, 1, 5, 10	48	↓ IBMX-induced melanogenesis	↓ Tyrosinase enzyme activity, protein and mRNA	Koo et al., 2008
		SK-MEL-2	IC50 = 14.4	24	↓ Proliferation	↓ DNA topoisomerase I	Lee et al., 2007