Table 2.

Anticancer effects of betulin and betulinic acid based on in vivo studies.

Type of Cancer	Animal Models	Effects	Mechanisms	Dosage	Duration	References
Oral squamous	Balb/c nude mice injected with KB cells (1 × 107 cells per mouse)	Inhibited the increase in tumor volume	↓ p53 in implanted tumor, ↓ STAT3 signaling, ↓ p- STAT3 in tumor tissues declined	50, 75 and 150 mg/kg	21 days	[156]
Colorectal	BALB/c nude mice xenografted with HCT116 cells (1 × 107 cells per mouse)	Inhibits metastasis	↓ MMP-2, ↓ Ki-67, ↑ caspase-3	0, 10, and 20 mg/kg	21 days	[180]
Gastric	BALB/c nude mice xenografted with SNU-16 cells (1 × 107 cells/mouse)	Delay tumour growth and inhibit pulmonary metastasis	↓ tumour weight, ↓ number of metastatic nodules, ↓ Ki-67 ↓ MMP2	40 mg/kg	21 days	[181]
Breast	Adult orange zebra danio fishes	Anti-angiogenesis	↓tail fin regrowth	Betulin suspension (BetS) (5 mg/g of betulin) and Group III – BeTNS (5 mg/g of betulin)	15 days	[160]
Breast	Balb/c-nu/nu mice subcutaneously injecting MDA-MB-231 cells (5 × 106)	Inhibited tumor growth	↓ Body weight loss, ↑ apoptosis ratio, ↓ Ki67 expression, ↑ expression of GRP78, ↑ CHOP	BA 250 mg/kg + taxol 10 mg/kg	24 days	[129]
Breast	Balb/c nude mice xenografted with MDA-MB-231 cells (2 × 105)	Inhibits metastasis	↓ MMP-2 & 9, ↓ vimentin, ↑ E-cadherin, ↑ GRP78, ↓ β-catenin, ↓ c-Myc	125 and 250 mg/kg	28 days	[161]
Hepatocellular	NOD/SCID mice implanted subcutaneously with 100 μL HepG2 cells suspensions (1 × 107 cells/mouse)	Reduces tumour growth	↓ Ki-67 positive cells, ↓ MMP-2 positive cells, ↓ cancer cell proliferation, ↓ Extents of metastatic nodules, ↓ lung weights	10 mg/kg	18 days	[171]
Renal	BALB/c nude mice injected with 786-O cells (1 × 106 cells per mouse)	Inhibits metastasis	↓ Ki67-positive cells, ↓ MMP9-positive cells,	0, 5, and 10 mg/kg	15 days	[172]
Ovarian	BALB/c nude mice injected with SKOV3 cells (5 × 106 cells)	Inhibits tumor growth and Inhibited metastasis	↓ EMT process, ↓ Ki-67+ cells, ↓ MMP-2+ cells	40 mg/kg	21 days	[176]