Prophylactic and therapeutic roles of oleanolic acid and its derivatives in several diseases

Table 7  In vivo anticancer effects and related mechanisms of action of oleanolic acid and its natural and synthetic derivatives (2014-2020)

Disease model/ physiology	Effect	Mechanism		Compound	Dose/IC50 /Ki.	Ref.
		↑↑↑	↓↓↓
Liver, lung and prostate cancer	Inhibits proliferation and induces apoptosis	cPARP-1,	pAKT, NF-κB, pmTOR	OA-Xs	7.5 mg/kg·d; d	[118]
PC3 prostate	Inhibits proliferation and induces apoptosis	HIF-1a, NAC-1	SENP-1	OA-Xn	10 mg/kg·d; 20d	[119]
Colorectal cancer mouse xenograft model	Induce apoptosis	BAX, P21, P53	BCL-2, CYC-D1, CDK-4, AKT p70S6K and MAPK	OA	16 mg/kg·d, 16d	[120]
Gastric cancer	Induce autophagy	pAMPK	pmTOR, pPI3K, AKT, pERK1/2, P38, pmTOR	OA	100 mg/kg·d; 7d	[121]
Kras G12D/+ ;Pdx-1-Cre (KC) pancreactic cancer	Inhibits infiltration		IL-6, CCL-2, VEGF, G-CSF	CDDO-imidazolide	25 or 100 mg/kg diet, 4 or 8 wk	[122]
Lung carcinoma	Inhibits proliferation	miR122, HNF-1a, HNF-3b, HNF-4a, HNF-6	CCNG-1, MEF-2D	OA	40, 120 mg/kg·d; 4 wk	[123]
Ovarian and endometrial cancer	Inhibition of profiferation	PARP, BCL-2, CASP-8,-3, -7.		OA-Xs	10-40 mg/kg·d; 21 d	[124]
Prostate cancer	Cell cycle arrest		AKT/mTOR, pAKT, pmTOR	OA-Xs	8.5-17 mg/kg·d; 21 d	[125]

NF-κB: Nuclear factor-κB; OA: Oleanolic acid; OA-Xn: Natural derivatives of oleanolic acid; OA-Xs: Synthetic derivatives of oleanolic acid; CDDO: 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid; HNF: Hepatocyte nuclear factor; ERK: Extracellular-signal-regulated kinase.