Table 3.

The Dosage of Pristimerin to Exert Antitumor Effects in vivo and in vitro

Cancer type	Time	Dose and administration (IC50 value or inhibition rate)	Mechanisms	References
Breast cancer	24h	0.6μM significantly caused MDA-MB-231 and MDA-MB-468 cells death	Induced apoptosis and autophagy via activation of ROS/ASK1/JNK pathway	[5]
	72h	0.42–0.61 µM IC50 against MDA-MB-231	Resulted in a rapid release of cytochrome c from mitochondria, which preceded caspase activation and the decrease of mitochondrial membrane potential but not significantly altered the protein level of Bcl-2 family members, nor did it induce Bax translocation	[19]
	2 days	1 mg/kg, i.p.	Induced apoptosis and an incomplete autophagy	[26]
	24h	10µM caused 40–60% MDA-MB-231 cell each	Combination of pristimerin and paclitaxel additively induced autophagy in human breast cancer cells via ERK1/2 regulation	[27]
	2h	0.125–1μM significantly reduced the relative proteasome activity in MDA-MB-231 cells	Inhibited tumor migration and invasion by inhibiting proteasomal activity and increasing the levels of RGS4	[31]
	24h	2.4 μM IC50 against SKBR3	Decreased HER2 expression, fatty acid synthase and inhibited the Akt, MAPK, and mTOR signaling pathways to affect metastasis and apoptosis	[33]
	48h	0.5 μM wholly decreased the MDA-MB-231 cell viability	Inhibited cancer progression and EMT reversion by suppression of integrin β3	[32]
	2 days	3 mg/kg, s.c.	Reduced tumor volume and weight, inhibited tumor growth and angiogenesis associated with downregulation of VEGF	[43]
Colorectal cancer	72h	1.11 μM IC50 against HCT-116	Downregulated PI3K/AKT/mTOR pathway and its subsequent downstream p70S6K and E4-BP1 proteins.Inhibited tumor growth and induced apoptosis	[8]
	24h	0.98 μM IC50 against HCT-116	Induced apoptosis through activation of ROS/ER stress-mediated noxa and elevated the expression of ER stress-related proteins, resulting in activation of the IRE1a and JNK signal pathway through the formation of the IRE1a-TRAF2-ASK1 complex	[25]
	48h	0.83 μM IC50 against HCT-116
	2 days	1 mg/kg, i.p.	Inhibited NF-κB signaling pathway	[40]
Prostate cancer	72h	1.25–5μM caused 47–73% LNCaP and PC-3 cell death	Induced apoptosis through ubiquitin-proteasomal degradation of antiapoptotic survivin	[14]
	24h	24h 0.5–5μM caused 30–85% PC-3 cell death	Induced apoptosis by targeting the proteasome and inhibited the proteasomal chymotrypsin-like activity	[21]
	24h	5μM caused 40% C4-2B cell death
	8h	5μM gradually decreased LNCaP cell to complete ablation
	72h	1.25 μM caused 55% LNCaP cell death	Induced apoptosis in prostate cancer cells by down-regulating Bcl-2 through ROS-dependent ubiquitin-proteasomal degradation pathway.	[22]
		1.25 μM caused 47% PC-3 cell death
	36h	0.4 μM can inhibit the proliferation of PC-3 cells and the effect was more marked at 0.8 μM	Inhibited the hypoxia-induced proliferation, invasion, spheroid formation, colony formation, stem cell characteristics and EMT protein expression	[34]
	24h	7.5 ×103 cells/µL 1.6 µM pre-treated PC-3 cells	Inhibited bone metastasis by targeting PC-3 stem cell characteristics and VEGF-induced angiogenesis. Inhibited the bone destruction by the invasion of the tumor and reduced the tumorigenic potential of bone metastasis.	[35]
	4h	1μM caused 55% SPHK-1 cell death	Inhibited HIF-1a through the SPHK-1 pathway.	[36]
Cholangiocarcinoma	——	The cell viability was lowest at 20μM	Lowered the expression of apoptosis related proteins (Bcl-2, Bcl-xL, and procaspase-3), but increased the Bax expression Resulted in the G0/G1 cell cycle arrest, reducing the expression of cell cycle related proteins (cyclinE, CDK2, and CDK4), and increased the expression of autophagy related proteins (LC3)	[7]
OSCC	72h	0.70 μM IC50 against CAL-27	Induced apoptosis via G1 phase arrest and MAPK/Erk1/2 and Akt signaling inhibition	[13]
		0.73 μM IC50 against SCC-25
Hepatocellular carcinoma	72h	1.44 μM IC50 against HepG2	Generated ROS, induced release of cytochrome c, and down-regulated EGFR protein	[49]
Pancreatic cancer	24h	0.65 μM, 0.97 μM, 1.26 μM, IC50 against BxPC-3, PANC-1, and AsPC-1, respectively	Caused G1 arrest, induces apoptosis, and enhances the chemosensitivity to Gemcitabine.Inhibited translocation and DNA-binding activity of NF-kB	[15]
	48h	0.28 μM, 0.34 μM, and 0.38 μM IC50 against BxPC-3, PANC-1, and AsPC-1, respectively
	72h	0.19 μM, 0.26 μM and 0.30 μM IC50 against BxPC-3, PANC-1, and AsPC-1, respectively
	72h	0.625~5 μM caused 52~85% MiaPaCa-2 cell death	Induced apoptosis through the inhibition of pro-survival Akt/NF-kB/mTOR signaling proteins and anti-apoptotic Bcl-2	[20]
	72h	0.625~5 μM caused 13~81% Panc-1 cell death
Cervical Cancer	72h	0.85–1.7 µM IC50 against HeLa, CasKi, and SiHa	Induced Mitochondrial Cell Death by ROS-dependent activation of Bax and Poly (ADP-ribose) Polymerase-1	[17]
Ovarian carcinoma	72h	1.25 µM caused 44% OVCAR-5 cell death 1.25 µM caused 28% MDAH-2774 cell death 2.5 µM caused 27% OVCAR-3 cell death 2.5 µM caused 36% SK-OV-3 cell death	Inhibited AKT/NF-k B/mTOR signaling pathway.Inhibited the expression of NF-kB-regulated antiapoptotic Bcl-2, Bcl-xL, C-IAP1 and survivin.	[23]
Leukemia	72h	1.49 μM IC50 against K562	Induced autophagy-mediated cell death through the ROS/JNK signaling pathway	[6]
	72h	0.61 μM IC50 against HL-60	Inhibited DNA synthesis.	[18]
ESCC	2 days	1 mg/kg, i.t.	Inhibited proliferation, migration, and invasion via suppressing NF‐kB pathway	[39]
Esophageal cancer	72h	1.98 μM IC50 against EC9706	Decreased the protein expression of CDK2, CDK4, cyclin E, and Bcl-2 and increased the expression of CDKN1B Elevated the ratio of LC3-II/LC3-I	[28]
	72h	1.76 μM IC50 against EC109
Lung cancer	——	0.8 mg/kg pristimerin and 2 mg/kg cisplatin, s.c.	Enhanced the effect of cisplatin by inhibiting the miR−23a/Akt/GSK3β signaling pathway and suppressing autophagy	[30]
	16 days	0.2mg/kg pristimerin and 0.4mg/kg pristimerin, s.c.	Inhibited angiogenesis targeting Shh/Gli1 signaling pathway	[37]
Glioma	——	2μM remarkably inhibited U373	Targeting AGO2 and PTPN1 expression via miR-542-5p	[41]
	6h	5.0 μM IC50 against U87	Triggered AIF-dependent programmed necrosis in glioma cells via activation of JNK.	[48]
		4.5 μM IC50 against U251
	2 days	1 and 3 mg/kg, s.c.
Uveal melanoma	24h	30μM, only 20% toxicity	Induced apoptotic cell death through inhibition of PI3K/Akt/FoxO3a pathway.	[45]