The Anticancer Potential of Maslinic Acid and Its Derivatives: A Review

Figures & data

Figure 1 Chemical structure of MA.

Figure 2 Anticancer properties of MA and its corresponding IC₅₀ values.

Note: Created with BioRender.com.

Table 1 The Anticancer Effects of MA in vivo

Cancer Types	Animals	Models	MAConcentrations	Route of Administration	Administration Times	Effects	References
Colorectal cancer	4-week-old male mice	ApcMin/+ intestinal polyp mouse model	100 mg MA/kg feed	Diet supplemented	6 weeks	Reduced total intestinal polyp formation by 45%	[^Citation41]
	6-week-old male C57BL/6J mice	Azoxymethane (AOM)/dextran sulfate sodium (DSS) mice model	10 mg/kg and 30 mg/kg day-1	Orally	40 days	Protects against DSS-induced acute colitis, attenuated the increase of tumors. ↓IL-6, ↓TNF-α, ↑IL-10,	[^Citation42]
	5-week-old male BALB/c nude mice	HCT116 xenograft model	10 mg/kg and 30 mg/kg day-1	Orally	17 days	Suppressed the tumorigenesis, ↓p-mTOR, ↓p-4EBP1, ↓p70S6K,↑p- AMPK.	[^Citation42]
Leukemia	5-week-old male BALB/c mice	WEHI-3 xenograft model	0, 8, 16, 32 mg/Kg	Intraperitoneal injection	2 weeks	Increase immune responses: enhanced macrophage phagocytosis and NK cell activities	[^Citation80]
Pancreatic cancer er	4–5 week-old athymic nu/nu male mice	Panc-28 xenograft model	10, 50 mg/kg MA every 2 day	Subcutaneous injected	36 days	Suppressed pancreatic tumor growth, induced tumor apoptosis, and inhibited NF-B-regulated anti-apoptotic gene expression, such as Survivin and Bcl-xl.	[^Citation112]
Gallbladder cancer	6-week-old athymic nu/nu male mice	EH-GB2 xenograft model	30 mg/kg MA every 2 days+GEM	Subcutaneously injected	30 days	Inhibitory tumor volume, and decreased NF-κB-regulated gene products expression.	[^Citation90]

Table 2 The Anticancer Effects of MA in vitro

Cancer Types	Cell Lines	MA Concentration	IC50	Exposure Time	Effects	References
Colorectal cancer	Caco-2 colon cancer cells	0 −100 μg/mL	39.7±0.4μg/mL	72h	↑caspase-8 /caspase-3, ↑ caspase-9, ↑JNK, ↓Bid, ↓Bcl-2	[^Citation43]
	HCT116, SW480 cells	5, 10, 20, 30μM	SW480: 19.04μM HCT116: 18.48 μM	12h	↑cleaved caspase-3, −9, ↓Bcl-2; ↑p- AMPK, ↑(AMP+ADP)/ATP; ↓p-mTOR, ↓p-4EBP1 and p70S6K	[^Citation42]
	Caco-2 colon cancer cells	IC50: 40.7μg/mL IC80: 56.8 μg/mL	40.7μg/mL	72h	↑cleavage of caspases −8 and −3, ↑ t-Bid, ↑ cytochrome C release	[^Citation44]
	HT29 cells	0 −100 μg/mL	39.7±0.4μg/mL;	72h:	↓Bcl-2,↑Bax, ↑ cytochrome C, ↑Caspase-9 and Caspase-3	[^Citation45]
	HT29 cells	3.75, 7.5, 15 and 30 μM	30 μM	3, 12, 24, 48, 72 h	–	[^Citation46]
Melanoma	B16F10 cells	10–100µg/mL	–	24 h	↑ROS	[^Citation49]
	B16F10 and A10 cells	IC50/4, IC50/2, IC50,2·IC50	42.3μM	–	↓ SOD, ↓GSTs, ↓GSH-Px.	[^Citation50]
Lymphoma	Raji cells	12.5, 25, 50, 100 μM	100 μM	8h	↓COX-2, ↓NF-κB, ↓AP-1	[^Citation52]
	Raji cells	IC50: 0.1μm/mL	100 μM	72 h	–	[^Citation54]
	Raji cells	12.5, 25, 50, 100 and 200μM	–	4, 8, 16, 24 48, and 72 h	↓dUTPase, ↓stathmin, ↓cyclin D1, ↑p21 protein, ↓NF-κB	[^Citation53]
Lung cancer	A549 cells	0, 9, 12, 15, 18, 21μg/mL	–	24 h	↓caspase-3, −8 and −9, ↑cleaved caspase-3, −8 and −9. ↑Smac, ↓ c-IAP1, c-IAP2, X-linked inhibitor of apoptosis protein, ↓(XIAP) and Survivin	[^Citation58]
	A549 cells	0, 4, 8, 16, 32, 64 μM	–	–	↓ Bcl-2, ↓Na+-K+-ATPase activity, ↑caspase-3/8, ↑cytochrome c, ↓HIF-1α, ↓VEGF, ↓ survivin, ↓iNOS	[^Citation59]
Triple negative breast carcinoma	MDA-MB-231, MDA-MB-468, MCF7 cells	30–50 µM	–	24h	↓ CDK4, ↓ CDK2 (TNBCs) ↑ CDK2 (MCF7); ↑ Bax, ↓ BCL2, ↑ Bax/Bcl-2 ratio. ↓survivin	[^Citation64]
	MDA-MB-231 cells	0–20µM	–	24h	MA+DOC: ↓MELK, ↓FoxM1, ↓ FoxM1, ↓ ABCB1	[^Citation65]
Ovarian cancer	A2780 cells	1, 24, 60 μM	–	6, 12, 24h	–	[^Citation104]
Gastric Cancer	SGC-790 cells	0–50μM	33.09±3.15	6, 24h	↑p38 MAPK, ↑ caspase	[^Citation69]
	MKN28 cells	0, 0.1, 1, 10 µM	8.45 µM	24h	↓Bcl2, Bax and Bad; ↓IL-6/JAK/STAT3 signaling cascade: (↓ p-STAT3 and JAK2, ↓ IL-6	[^Citation70]
Pancreatic cancer er	Panc‐28 cells	6.25, 12.5, 25, 50, 100, and 200 μM	49.2±0.5 μM	48 h	↑LC3‐II/LC3‐I, ↑ Atg7, Atg16L, Atg5, Atg12 and Atg3, ↓p‐mTOR, ↑p‐ULK1(via ↑HSPA8)	[^Citation73]
	Panc-28 cells	10μM	–	6, 12, 24, 48 h	MA+TNFα ↑p65; ↓cell proliferation gene (Cyclin D1, CO-2 and c-Myc), ↓ apoptosis (Survivin), Bcl-2, Bcl-xl, XIAP, IAP-1), ↓ invasion (MMP-9 and ICAM-1), ↓ angiogenesis (VEGF)	[^Citation112]
Bladder cancer	T24, 253J, MRC-5 cells	0–100μM	T24:32.98 ± 4.06µM 253J:71.83 ± 5.42µM MRC-5:328.75 ± 40.64µM	48h	↑ P38 MAPK	[^Citation77]]
Prostate canc	DU145 cells	0–25μM	–	24h	↓uPAR, E-cadherin, VEGF and MMP; ↓ HIF-1a, ↓ Akt and ERK	[^Citation84]
Renal cancer	RCC, SN12K1, HUVEC, PTEC cells	0–100μM	–	24h	↓VEGF	[^Citation87]
Gallbladder carcinoma	–EH-GB1, EH-GB2 and GBC-SD cells	10–200μM	–	0, 12, 24, 48h	MA+ GEM ↓NF-κB, ↓ cyclin D1, Bcl-2, Bax, MMP-2 and MMP-9. .	[^Citation90]
Astrocytoma	1321N1 cells	1–50μM	25μM	24h	↑ caspase-3, ↑ ROS	[^Citation93]
Adenoid cystic carcinoma	ACC-2 and ACC-M cells	0–100μM	ACC-2: 43.68 μM, ACC-M: 45.76 μM,	24h, 48h, 72h	↑[Ca2+]^i, ↑p38 MAPK phosphorylation, ↑caspase-3	[^Citation117]
Pheochromocytoma	PC12 cells	1, 3, 5, 10 μM,	–	24h	↑ LC3-I/II conversion, ↓Beclin1	[^Citation96]
Neuroblastoma	SHSY-5Y cells	0, 5, 10, 20, 40, 80µM	–	12h, 48h	↑ ROS, ↓MAPK/ERK	[^Citation97]
Soft tissue sarcomas	SW982 and SK-UT-1 cells	10–100 μM	–	24 h	MA+DXR: ↓ MRP-1	[^Citation98]

Figure 3 Chemical structure of MA derivatives.

Figure 4 Partial molecular pathways involved in the anti-cancer mechanism of MA.

Note: Created with BioRender.com.

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