Table 2.

Antineoplastic effects and underlying mechanisms of action of XH based on in vitro experiments.

Cancer Type	Cell Line	Effects	Mechanisms	Conc.	Reference
Breast cancer	Hs57BT and MDA-MB-231	Decreased cell viability, cell invasion and proliferation	None	4.78–6.7 µM	[57]
	MDA-MB-231	Decreased cell viability	↑Caspase-3; ↑caspase-9; ↓Bax	10 and 20 µM	[56]
	MCF-7	Decreased proliferation	↓ALP isoenzymes	10 µM	[50]
	Adriamycin-resistant MCF-7	Decreased cell viability, stemness, and increased radio- and chemosensitivity	↑Apoptosis; ↑γ-H2AX; ↓STAT3; ↓MDR1; ↓EGFR	10 µM	[59,68]
Cervical cancer	Ca Ski	Decreased proliferation	↑Apoptosis; ↑caspase-3; ↑caspase-8; ↑caspase-9; ↑cell cycle arrest; ↑p53; ↓XIAP	59.96 µM	[61]
Choliangiocarcinoma	KKU-M139 and KKU-M214	Decreased cell growth	↓STAT3	20 and 50 µM	[63]
Colon cancer	40-16 colon cancer	Decreased proliferation	None	4.1, 3.6 and 2.6 µM	[65]
	HT-29 and CDD-18Co	Decreased cell viability	↑Apoptosis; ↑caspase-3; ↑caspase-9; ↓cyclin B1; ↓MEK/ERK; ↓G2/M phase of cell cycle	10 and 100 µM	[69]
	HT-29	Decreased cell viability	None	48 and 72 µM	[70]
	HCT115	Decreased proliferation	↓ABCC 1,2,3; ↓ABCB1	10.2 µM	[66]
Colorectal cancer	FHC, CCD841, CoN, HT29, SW480, LOVO, HCT116 and SW620	Decreased cell proliferation, cell viability, and colony formation	↑Apoptosis; ↓HK2; ↓glycolysis; ↓EGFR-Akt	25 µM	[71]
Esophageal cancer	KYSE30, KYSE70, KYSE410, and KYSE450	Suppressed proliferation, foci formation, and anchorage-independent colony growth	↓Apoptosis; ↑cell cycle arrest (G1 phase); ↓Bax; ↓cyclin D1; ↓cyt. c; ↓cleaved-PARP; ↓Bcl-2; ↓cyclin D3; ↓KRT18	0.3, 0.6, 1.25, and 2.5 µM	[72]
Glioblastoma	U87 glioblastoma	Decreased cell viability	↑Apoptosis; ↓IGFBP2/Akt/Bcl‑2; ↑mIR-204-3p; ↑ERK/c-Fos	25 µM	[73]
	T98G	Decreased cell viability	↑Apoptosis; ↑ROS; ↑p-p38; ↓p‑ERK1/2; ↑cleavage of PARP ↓caspase-3; ↓caspase-9	20 µM	[74]
	LN229, T98G and U87-MG	Inhibited proliferation, viability, and colony formation	↓Akt-GSK3β-FBW7-c-Myc protein, ↓HK2 protein	2, 5, and 10 µM	[75]
Hematological cancers	Acute lymphoblastic leukemia L1210 and adriamycin-resistant L1210	Decreased cell viability, invasion and migration	↑Apoptosis; ↓Akt; ↓FAK; ↓NF-κB	2.5, 5, and 10 µM	[76]
	Chronic myeloid leukemia KBM-5	Suppressed invasion	↑Apoptosis; ↓IKK activity; ↓p65 nuclear translocation; ↓IκBα degradation and phosphorylation; ↓TRAF-2; ↓cIAP-1; ↓cIAP2; ↓survivin; ↓XIAP; ↓Bcl-xL	50 µM	[77]
	Bcr-Abl+ myeloid leukemia cells K562	Decreased adhesion to endothelial cells, cell viability, and invasion	↑Apoptosis; ↓MMP-2; ↓Bcr-Abl; ↑p21; ↑p53	2.5, 5, and 10 µM	[78]
Laryngeal cancer	RK33 and RK45	Decreased cell viability	↑Apoptosis; ↑caspase-3; ↑caspase-8; ↑caspase-9; ↑p53; ↑p21; ↓cyclin D1; ↓ERK1/2	12.3 and 22.5 µM	[79]
	SCC4	Decreased proliferation	↑Apoptosis; ↑PARP; ↑p53; ↑AIF; ↓Bcl-2; ↓Mcl-1	20, 30, and 40 µM	[80]
Liver cancer	HepG2	None	None	10 µM	[81]
	Huh7, Hep3B, SK-Hep1, and HepG2	Decreased colony forming, cell viability and confluency ability	↓HES1; ↓Notch1 pathway	5 µM	[82]
	Hep3B and HA22T/VGH	None	None	108 and 166 µM	[83]
Melanoma	B16	Decreased IBMX-induced melanogenesis	↓Tyrosine enzyme activity	0.5, 1.5, and 10 µM	[84]
	SK-MEL-2	Decreased proliferation	↓DNA topoisomerase 1	14.4 µM	[66]
Ovarian cancer	A-2780	Decreased proliferation	None	0.52 and 5.2 µM	[70]
	OVCAR3 and SKOV3	Decreased proliferation	↓Notch1 pathway; ↑p21; ↑cell cycle arrest	10, 20, and 30 µM	[85]
Oral squamous cell carcinoma	OSCC	Decreased cell viability and reversed radioresistance	↓Survivin; ↑mitochondrial apoptotic signaling; ↓Akt-Wee1-CDK1	1–5 µM	[86]
Pancreatic cancer	PANC1 and BxPC3	Decreased proliferation, viability, and colony formation	↑Apoptosis; ↓p-STAT3	5–100 µM	[87]
	BxPC3, MXPaCa2, and AsPC1	Inhibited cell proliferation	↓NF-κB; ↓VGEF ↓IL-8; ↓mRNA	0.5–25 µmol/L	[88]
Prostate cancer	Hormone-refractory AR−PC3	Decreased cell viability	↑Apoptosis; ↓activation of NF-κB	2.5–20 µM	[89]
	Hormone-sensitive AR+, hormone-refractory AR− PC3, LNCaP and DU145	Decreased cell viability	↑Apoptosis; ↓NF-κB; ↓p65; ↓p-Akt; ↓p-mTOR; ↓survivin; ↓Bcl-2	24 and 40 µM	[90]
	Hormone-refractory AR− PC3, DU145 PC3, DU145	Decreased proliferation, invasion, and migration	↓p-FAK; ↓p-Akt	2.5, 5, and 10 µM	[91]
Thyroid cancer	MTC (medullary thyroid cancer cells)	Decreased proliferation and malignant phenotype	↑ERK1/2 phosphorylation	10, 20, and 30 µM	[92]