Roles of conventional and complementary therapies in recurrent hepatocellular carcinoma

Table 3 Compounds and formulas for reducing hepatocellular carcinoma recurrence via inhibition of cancer stemness

Compound or Chinese herbal medicine or formula	Cell line/animal	Molecular mechanism	Effect	Ref.
Antrodia cinnamomea	Hep G2	↓CD133+	↓CSC	Su et al[89]
Tiliroside	Hep3B, SNU-449	↓CD133+. ↓Carbonic anhydrases XII. ↑E2F1/E2F3/Caspase-3 axis	↓Tumor sphere formation. ↓WInvasion and migration. ↓Stemness gene expression. ↑Apoptosis	Han et al[90]
8-bromo-7-methoxychrysin	SMMC-7721, MHCC97H-derived LCSLCs	↓CD133, CD44. ↓IL-6	↓CSC	Wen et al[91]
Curcumin	PLC/PRF5, WRL68, Huh7, KMCH, AFP-negative primary HCC cell line	↓CD117, EpCAM, CD133, RNF51, NANOG. ↓NF-κB	↓CSC	Marquardt et al[92]
Sophocarpine	HCC-LM3, MHCC-97H. BALB/c nude mice (4-wk, male, 0.4-6 g/kg, twice a week for 4 wk)	↓TGF-β. ↓CD133, CD90 and EpCAM	↓EMT. ↓CSC	Zhang et al[93]
Matrine	Hep3B, Huh7. BALB/c nude mice (-,-,10 mg/kg, daily for 3 wk)	↓EpCAM+/CD133+ cell number. ↓PI3K/AKT/mTOR pathway, AKT/GSK-3β/β-catenin pathway	↓Sphere formation. ↓Stem cell markers. ↑Mature hepatocyte markers	Liu et al[94]
Brucea javanica	HepG2 (HB-8065, wild-type p53), Hep3B (HB-8064, p53-null)	↓CD133, NANOG, EpCAM	↑Apoptosis. ↓Stem-like cells	Chen et al[95]
2-Ethoxystypandrone	Hep3B, HepG2, Huh7, Li-7, SK-Hep-1	↓STAT3 activation	↓Proliferation, ↑Apoptosis. ↓CSC	Li et al[96]
BRM270	HepG2 (CD133+), SNU-398. CRJORI:CD-1-5WM (6-wk, male, 5 mg/kg/day, daily for 12 wk)	↓CyclinD1/Bcl2 mediated c-Jun apoptotic pathway. ↓CD113	↓Proliferation, ↑Apoptosis. ↓CSC	Kumar et al[97]
Songyou Yin (consisted by Salvia miltiorrhiza, Astragalus membranaceus, Lycium barbarum, Crataegus pinnatifida and Trionyx sinensis)	MHCC97-H, Hep3B	↓CD90, BCRP, ALDH, CD44, EpCAM, vimentin, MMP-9. ↑E-cadherin	↑Oxaliplatin chemosensitivity. ↓Motility, invasion, and colony formation. ↓CSC	Jia et al[98]

Akt: Protein kinase B; ALDH: Aldehyde dehydrogenases; Bcl-2: B-cell lymphoma 2; BCRP: Breast cancer resistant protein; CD: Cluster of differentiation; COX-2: Cyclooxygenase-2; EpCAM: Epithelial cell adhesion molecule; GSK: Glycogen synthase kinase; HIF: Hypoxia-Inducible Factor; IL: Interleukin; MMP: Matrix metalloproteinase; mTOR: Mammalian target of rapamycin; NF-κB: Nuclear factor kappa B; PI3K: Phosphatidylinositol 3-kinase; RNF51: RING finger protein 51; STAT3: Signal transducer and activator of transcription 3; TGF: Transforming growth factor; VEGF: Vascular endothelial growth factor.