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. 2024 Jul 18;29(14):3388. doi: 10.3390/molecules29143388

Table 1.

Anti-cancer effects and mechanisms of A. membranaceus saponins.

Pharmacological Activity Components Models Administration Design Mechanisms Refs.
Inhibition of cell proliferation AS-IV HT29, SW480, BALB/c mice 25, 50 μM; 24 h;
20 mg/kg; 30 days; i.g.		 p21, Cyt C, and Omi↑ [34]
AS-IV CT26 10, 50, and 100 nM; 48 h B7-H3, Cyclin D1, and CDK4↓ [35]
AST HT29 94 μM; 24, 48, and 72 h; mTOR/NF-κB pathway↓;
PTEN↑		 [36]
CAG SNU1,
SNU16		 10, 30, and 50 μM; 8 h
SNU16: IC50 5 μM		 p-STAT3, STAT3, and JAK1/2↓;
caspase-3 and PARP cleavage↑		 [37]
Lupeol HEp2, UPCI 50 μM; 72 h;
HEp2: IC50 53.51 μM
UPCI: IC50 52.44 μM		 p53 and p16↑; Cyclin D1↓ [38]
AS-IV SW962 255 μM; 24 h Cyclin D1↓;
Bax, cleaved caspase-3, p21, and p53↑		 [39]
AS-IV U251 50, 75, and 100 μM; 24 h Ki67, PCNA, MMP-2, MMP-9, and MAPK/ERK pathway↓ [40]
AS-III MDA-MB-231, nude mice 13, 65, and 130 nM; 24, 48 h;
10, 20 mg/kg; 30 days; i.p.		 mTOR/NF-κB pathway↓ [41]
AS-IV A549 125 μM; 24 h;
A549: IC50 32.2 μM		 p-PI3K, p-AKt, and p-mTOR↓ [42]
AS-IV, NaAsO2 HepG2 4 μM NaAsO2, 1 μM AS-IV;
48 or 72 h		 PI3K/AKt/mTOR pathway↓ [43]
AS-IV SW620, HT116 0, 6, 12, 25, 62, and 126 nM;
24, 48, and 72 h		 miR-29c↑;
B7-H3 and NF- κB↓		 [44]
DS MCF7, AGS, MGC803,
Murine H22 hepatoma
allograft model		 5, 25, 50, and 100 μM; 48 h;
MCG803: IC50 19.96 μM, BGC823: IC50 3.13 μM,
AGS: IC50 24.19 μM,
MCF-7: IC50 16.95 μM
0.5, 2.5 mg/kg; 7 days; i.g.		 ROS production and LC3-II↑ [45]
Lupeol Y79,
WERI-Rb-1		 10, 20, and 40 μM; 24 h;
Y79: IC50 47.1 μM,
WERI-Rb-1: IC50 26.7 μM		 Bax/Bcl-2 and LC3 II↑;
Ki67, Bcl-2, and PI3K/AKt/mTOR pathway↓ 		[46]
Lupeol CD-1 mice 12, 24 mM;
30 min		 iNOS↑;
COX-2, and PI3K/Akt pathway↓		 [47]
AS-IV HSC-T6, HepG2, C57BL/6J 5, 10, and 20 μM; 24 h;
20, 40, and 80 mg/kg;
20 weeks; i.g.		 Nrf2/HO-1 and p-Smad3C/p21
pathway↑;
p-Smad3L/c-Myc pathway↓		 [48]
AS-IV SMMC7721, Huh7 6, 12, 25, 50, 100, 125, 150, 225, and 255 μM; 24 h;
20 μg/mL; 24 h		 miR-1505p↑;
β-catenin and CTNNB1↓		 [49]
Induction of apoptosis AS-IV HCC827, A549,
NCI-H1299		 15 and 30 nM; 48 h cleavage of caspase-3↑;
Akt/GSK-3β/β-catenin pathway↓ 		[50]
AS-IV HT29, SW480, BALB/c nu/nu mice 12, 25, and 50 μM; 24 h;
20 mg/kg; 30 days; i.g.		 Cyt C, Omi, and p21↑ [34]
AS-III MCF7,
MDA-MB-231,
nude mice		 13, 65, and 130 nM; 24, 48 h;
10, 20 mg/kg;
every two days, 30 days; i.p.		 mTOR/NF-κB pathway↓ [41]
HDG MCF7,
MDA-MB-231		 0.2, 0.8, 4.2, and 21.2 μM; 24 h; caspase-3 and caspase-9↑;
Apaf-1 and Cyt C↓		 [51]
Lupeol Oxaliplatin-
R LoVo,
nude mice		 0, 20, 50, 100, and 150 μM; 24 h;
LoVo: IC50 15 μM
150 mM; every two days,
12 days; i.p.		 ER stress↑; ABCG2↓ [52]
HDG LoVo cells 1.0, 2.0 μM; 24, 48 h;
LoVo: IC50 1.39 μM at 24 h and 1.17 μM at 48 h		 Bax, caspase-3, caspase-9, Bcl-2, procaspase-9, procaspase-3, and PARP↑ [53]
AS-IV MG63, 143B, BALB/c nu/nu mice 20, 40, 60, 80, and 100 μM; 48 h;
20 mg/kg; 28 days; i.g.		 cleaved caspase-8, cleaved caspase-3, cleaved PARP, Fas, and FasL expression↑ [54]
AS-IV SK-Hep1, Hep3B 0, 200, and 400 μM; 48 h cleavage of caspase-3, caspase-8, and caspase-9↑;
XIAP, MCL1, and CFLIP↓		 [55]
AS-IV HT29 75 μM; 1 h PTEN↑; reduce the binding activity of NF-κB to DNA, activate the activity of ERK 1/2 [36]
AMs MKN45, C57/BL female mouse 76–102 nM; 24 h;
250 mg/kg; 6 days; i.p.		 TLR4 and CD11c↑; IκB-αby↓ [56]
AST MGC803, MKN45,
HCT116,
MCF7, HepG2, HT29, Caco2, DLD1		 94, 125 μM; 24 h, 48 h;
HCT116: IC50 94 μM		 NAG-1, Egr-1, and PARP
cleavage↑;
PI3K/Akt pathway↓		 [57]
AS-IV SW962 255 μM; 24 h Bax, and cleaved caspase-3↑;
Bcl-2, Bcl-xl, and TGF-β1/FAK/Akt pathway↓		 [39]
DS A549 25, 50, 100, and 200 μM; 72 h;
A549: IC50 20.9 μM		 PARP and caspase-3↑;
EGFR and STAT3↓ 		[58]
AS DU145 20, 50, and 100 nM; 72 h IRE1, p-PERK, AFT4, AFT6, BiP, CHOP, and caspase-12 mRNA↑ [59]
AS-IV A549Cis, H1299Cis 3, 5, 10, and 20 nM; 24 h PERK, LC3 II/I ratio, GRP78, and Beclin1↓ [60]
Lupeol HEp2, UPCI 50 μM; 24h;
Hep-2: IC50 53.51 μM,
UPCI: IC50 52.44 μM		 p53 and p16↑; Cyclin D1↓ [38]
AS and CGA 4T1, EMT6, BT549,
MDA-MB-231, SPF-BALB/c mice		 2, 6 mM; 72 h;
4T1: IC50 6.7 mM, EMT6: IC50 5.6 mM, BT-549: IC50 7.3 mM, MDA-MB-231: IC50 1.8 mM
20 mg/g; 21 days; p.o.		 RTK, VEGF, EGF, IL-10, TGF-β, and CD34↓ [61]
AS-IV SMMC7721, Huh7 200 μM; 48 h IL11/STAT3 signaling↑;
lncRNA-ATB↓ 		[62]
Lupeol H1299, A549, H460, WI38 125 and 250 μM; 72 h PARP↑; EGFR and STAT3↓ [63]
HDG MCF7,
MDA-MB-231		 0.2, 0.8, 4.2, and 21.2 μM; 24 h caspase-3 and caspase-9↑;
Apaf-1 and Cyt C↓		 [51]
AS-IV ULM1,
ULM2,
SD rats		 1, 10, 50, 100, 200, 300, and
400 µM; 24 h;
ULM1: IC50 205.9 µM
ULM2: IC50 215.0 µM
0.5, 4 mg/kg; 10 weeks; i.p.		 IDO1↑;
PTEN/PI3K/Akt pathway↓		 [64]
DS MCF7, BGC823, MGC803,
Murine H22 hepatoma allograft model		 0.01, 0.1, 1, 3, 10, 30, and
100 mΜ; 48 h;
MGC803: IC50 19.96 μM
BGC823: IC50 3.13 μM,
MCF-7: IC50 16.95 μM
0.5, 2.5 mg/kg; 7 days; p.o.		 ROS production,
and LC3-II↑		 [45]
Lupeol MNNG/HOS, MG63 30 mM; 24 h miR-212-3p↑; HMGA2↓ [65]
HDG SNU1041, SNU1066, SNU1076, BALB/c nu/nu mice 50 and 100 μM; 72 h;
200 mg/kg; 35 days; i.p.		 cleaved PARP, cleaved caspase-3, and Bax↑;
Nrf2-ARE pathway↓		 [66]
Inhibition of cell migration and invasion AS-IV U251 25, 50, and 100 μM; 48 h vimentin, N-cadherin, β-catenin, Cyclin D1, and Wnt/β-catenin
pathway↓		 [67]
AS-IV Huh7, MHCC97-H 1, 6, 12, 62, and 125 μM;
24, 48, and 72 h		 E-cadherin↑;
vimentin, α-SMA, N-cadherin, and Akt/GSK-3β/β-catenin pathway↓		 [68]
AS-IV HCC827, A549,
NCI-H1299		 4, 8, 15, and 30 nM; 48 h cleavage of caspase-3 and Bcl-2↑; Bax and Akt/GSK-3β/β-catenin
pathway↓		 [50]
Lupeol U2OS 0, 5, 10, 15, 20, and 25 μM;
12 or 24 h		 uPA, MMP-2, MMP-9, N-cadherin, β-catenin, p38, and PI3K/Akt/GSK-3β pathway↓ [69]
AS-IV A549 5, 10, and 20 μM; 24 h MMP-2, MMP-9, integrin β1, and PKC-α-ERK1/2-NF-κB pathway↓ [70]
AS-IV SiHa, BALB/c nude mice 62, 255, and 1000 μM; 24 h;
SiHa: IC50 800.39 μM
120 mg/kg; 21 days; i.g.		 TGF-β1, N-cadherin, Vimentin, and E-cadherin↑;
MAPK and PI3K↓		 [71]
AS-IV A549 5, 10, and 20 μM; 24 h MMP-2, MMP-9, integrin β1, and PKC-α-ERK1/2-NF-κB pathway↓ [70]
AS-IV SW962 125, 255 μM; 24 h E-cadherin, TGF-β1, FAK, and Akt↓ [72]
AS-IV Immortalized mouse podocyte cell line, C57BL/6 J mice 25, 50, and 100 μM; 48 h;
40 mg/kg; 12 weeks; i.g.		 Nephrin, E-cadherin, and SIRT1↑;
NF-κB, TGF-β, N-cadherin, α-SMA, Beclin 1, and LC3 II↓		 [73]
AS-IV HGC27, MKN45,
nude mice		 10, 20, and 40 μM; 24, 48 h;
40 mg/kg; 21 days; i.p.		 EIF4A1↑
Regulate circDLST/miR489-3p/EIF4A1 axis. circDLST↓		 [74]
AS-IV SGC7901, MGC803 6, 12, 31, and 62 μM; 24 h miR-195-5p and miR-424-5p↑;
PD-L1↓		 [75]
AS-IV SW480 6, 12, 31, and 62 μM; 24 or 48 h miR-134↑; CREB1↓ [76]
AS-IV MCF7,
MDA-MB-231, MDA-MB-468, BALB/c nude mice		 25, 50, and 100 μM; 48 h;
20 mg/kg; every three days,
14 days; i.p.		 TRHDE-AS1↑;
MMP-2 and MMP-9↓		 [77]
AS-IV SMMC7721, Huh7 200 μM; 48 h lncRNA-ATB↓ [62]
SsaI B16F10, NIH/3T3, C57BL/6J male mice 25, 50, and 75 μM; 24 h α2, 3-linked sialic acids↓ [78]
SsaI MCF7,
MDA-MB-231		 5, 25, 50, and 100 μM; 48, 72 h; α2,3-sialylations and ST3Gal IV↓ [79]
AS-IV MDA-MB-231, BALB/c nude mice 12, 25, 38, and 50 μM; 24 h;
20 mg/kg; every three days,
6 weeks; i.p.		 p-ERK1/2, p-JNK, and Vav3↓,
Rac1 signaling↓		 [80]
Regulation of autophagy DS A549,
NCI–H460, NCI–H23,
L132,
female Wistar		 25, 50, 100, and 200 μM; 24 h;
2.5, 10 mg/kg; 28 days; i.g.		 MDA, CA 15-3, TC, TG, and HDL-C↓ [81]
Isoalantolactone MDA-MB-231 1, 2, and 4 µM; 24 h MMP-2, MMP-9,
p38, MAPK, NF-κB, and p65↓		 [82]
AS-IV THP1, BALB/c nude mice 5, 10, 25, 50, and 100 μM; 24 h;
40 mg/kg; 20 days; i.p.		 Akt/Foxo1 and TGF-β↓ [83]
Enhance cellular immunity AS-IV A549, H1975, BALB/c nude mice 20 mg/kg; 20 days; p.o. MCM5/HDAC1, HDAC1, and MCM5↓ [84]
AS-III bEnd.3 10, 100, and 1000 nM; 24 h EGFR, ERK1/2, p38, and AKT↑
Inhibit PMA-induced EPCR shedding through MAPKs and PKC pathway.		 [85]
AS-IV HUVECs,
SD rats		 10, 20, 40, 80, and 160 μM; 18 h;
20, 50 mg/kg; 2 weeks; i.g.		 VEGF and PTEN/PI3K/Akt
pathway↑		 [86]
AS-II Bel7402,
Bel7402/FU		 0, 40, 80, 160, and 320 μM; 48 h LC3-II, Beclin-1, and MAPK/mTOR pathway↓ [87]
Astragalus–Scorpion LNCap, BALB/c nude mice A (1.17, 2.54, 3.9 g/kg);
S (0.39, 0.585, 0.78 g/kg);
4 weeks; i.g.		 GDPD4-2↑;
PI3K, Akt, and mTOR↓		 [88]
AS-IV SiHa, HeLA, BALB/c nude mice 5, 25, and 50 μM; 12 h;
12.5, 25, and 50 mg/kg; 35 days; i.g.		 DCP1A and TMSB4X↑;
LC3I/II↓		 [89]
AS-IV A549, H1299, A549cis, H1299cis 3, 5, 10, and 20 nM; 24 h PERK, LC3 II/I ratio, GRP78, and Beclin1↓ [60]
AS-IV RAW264.7 31, 62, and 125 μM; 24 h NLRP3↑;
IL-1β, IL-18, ROS, and TLR4/NF-κB pathway↓		 [90]
AS-IV SW962 125, 255, 510, 765, and 1020 μM;
24 h		 Induce G0/G1 phase arrest. TGF-βRII and Smad4↑ [39]
AS-IV SD rats 40, 80 mg/kg; 7 days; p.o. caspase-1, IL-1β, and IL-18↑;
NLRP3↓		 [91]
AS-IV Kunming mice,
the human lung fibroblasts cell line		 6, 12, 25, 50, 100, 200, and
400 μM; 24 h;
50, 100, and 200 mg/kg; 8–35 days; i.g.		 LC3B-II/LC3B-I ratio↑;
Col-I, Col-II, ATG7, Ras, Raf, MEK, ERKs, CD3 T cells, and CD68 T cells↓		 [92]
DS LNCap, PC3 5, 10, 20, 40, and 80 μM; 48 h cleaved caspase-3, cleaved caspase-9, Bax, LC3II/LC3I ratio, Beclin 1, and JNK↑ [93]
AS-IV A549 1, 25, 62, and 125 nM; 24 h CTLs↑; Tregs, IDO, and Akt/mTOR pathway↓ [94]
Combination therapy AS-IV A549, H1299, THP1, C57BL/6 J 80 nM; 48 h;
40 mg/kg; 21 days; i.g.		 AMPK, IL-13, and IL-4↓;
suppress M2 polarization of macrophages.		 [95]
AS-IV THP1, SKOV3 1, 6, and 12 μM; 24 h TGF-β, MMP-9, IL-10, HMGB1, and TLR4↓ [96]
AS-IV THP1, HeLa, SiHa 20, 40, 60, and 80 μM; 24 h;
HeLa: IC50 56.70 μM
THP1: IC50 85.34 μM		 CD163, IL-10, TGFβ, CD206, p-Smad2, and p-Smad3↓ [97]
AS-III CT26, BALB/c mice 4, 12, 20, and 40 nM; 48 h;
50 mg/kg; 2-day intervals
five times; i.v.		 NKG2D, Fas, IFN-γ, and T-Bet↑ [72]
Lupeol N87, BGC823, HGC27 1, 2, 4, 7, 14, 29, 58, 116, 232, and 464 μM; 72 h PFP, CD107a, IFN-γ, Wnt/β-catenin, PI3K/Akt, NK cells, NO, and TLR4/NF-κB pathway↑ [98]
AS-IV RAW264.7 31 to 125 μM; 24 h p38, ERK, and JNK↓ [99]
AS-IV SD rats 50, 100 mg/kg; 10 weeks; p.o. p53 and TP53↑;
MCT1, MCT4, HIF-1α, and CD147↓		 [100]
AS-IV BGC823 10, 20, and 40 μM; 72 h SOX2, NANOG, and miR-214↑; GCAFs and miR301a↓ [101]
AS-IV 3LL-luc, C57BL/6 40 mg/kg; 4, 8, and 12 days; p.o. CTLs↑;
Tregs, IDO, and Akt/mTOR
pathway↓		 [94]
AS-IV CT26, BALB/c female mice 10, 50, and 100 nM; 48 h;
15 mg/kg;
once every three days,
three times; i.p.		 B7-H3, CyclinD1, and CDK4↓ [35]
AS-IV SiHa, HeLa 5, 25, and 50 μM; 12 h;
HeLa: IC50 0.49 ± 0.03 mM,
SiHa: IC50 0.27 ± 0.03 mM;
12.5, 25, and 50 mg/kg; 35 days; i.g.		 DCP1A and TMSB4X↑;
LC3I/II↓		 [89]
AS-IV THLE2,
Huh7, SMMC7721, BALB/c nude mice		 12, 25, 50, and 100 μM; 4 h;
50, 100, and 150 mg/kg;
40 days; i.g.		 CNDP1↑;
PD-L1 and miR-135b-5p↓		 [102]
AS-IV/β-CD IC CTLL2, 4T1, NIH3T3, BALB/c nude mice 0.6, 1.2, 2.4, 4.8, and 9.6 μM;
24 h;
1.2, 1.6 mg/kg; 6 days; i.p.		 SOD↑; MDA↓ [103]
AS-IV SW620, HCT116 6, 12, 25, 62, and 125 nM;
48 h		 miR-29c↑; B7-H3, and NF- κB↓ [44]
AS-IV A549cis, H1299cis 2, 5, 10, and 20 nM; 24 h PERK, LC3 II/I, GRP78, and
Beclin1↓		 [60]
HDG NCI-H1299, NCI-H1975, BALB/c nude mice 50 μM; 4 or 24 h;
NCI-H1299: IC50 101.4 Nm, NCI-H1975: IC50 22.61 nM
25 mg/kg; 11 days; i.h.		 LC3-II/LC3-I ratio↑; p62↓ [104]
AS-II Bel7402,
Bel7402/FU		 40, 80, 160, and 320 μM; 48 h; LC3-II, Beclin-1, and MAPK/mTOR pathway↓ [87]
AS-IV MG63, 143B, BALB/c nu/nu mice 20, 40, 60, 80, and 100 μM; 48 h;
20 mg/kg; 28 days; i.g.		 cleaved caspase-8, cleaved caspase-3, cleaved PARP, Fas, and FasL expression↑ [54]
AS-IV LNCap, PC3 10 μM; 72 h;
40 mg/kg; 24 days; i.p.		 E-cadherin↑;
p-IĸB, p-AKT, p-p65, N-cadherin, and Vimentin↓		 [105]
AS-IV A549, H1975, BALB/c nude mice 20 mg/kg; once every two days,
20 days; i.g.		 MCM5/HDAC1, HDAC1, and MCM5↓ [84]
AS-IV SW480 0, 6, 12, 31, and 62 μM;
24 or 48 h		 miR-134↑; CREB1↓ [76]
AS-IV A549, HCC827,
NCI-H1299		 1, 3, 6, 12, 25, and 50 nM; 48 h B7-H3↓; increase cisplatin
cytotoxicity		 [106]
AS-IV HCT116, SW480, NCM460 3, 6, 9, 12, and 18 nM; 48 h NOTCH3↓ [107]
AS-IV NCI-H1299, HCC827, A549 3, 7, 15, and 30 nM; 48 h Increase gefitinib sensitivity. SIRT6↑ [108]
AS-IV MCF7,
MCF10A, MDA-MB-231		 10, 20, 30, 40, 50, 60, 70,
80, and 90 μM; 48 h		 eNOS/NO/ONOO−
pathway↑;
phosphorylation of CAV-1 and ERK/JNK↓		 [109]
AS-IV HepG2, H22, BALB/c nude mice 0.4, 4, and 40 μM; 24 h;
50 mg/kg; 14 days; p.o.		 MRP2↓ [110]
AS-IV Bel7402, Bel7402/FU 0.1, 0.2, 0.4, and 0.8 mM; 48 h P-gp and mdr1↓ [111]
AS-IV Bel7402/FU 0.1 mM; 24 h JNK, c-Jun, and APD-1 DNA binding activity↓ [112]
AS-IV 4T1, EMT6, BT549,
MDA-MB-231, SPF- BALB/c nude mice		 2.5 and 3 mM; 1.6 and
2.5 mM; 2 and 2.5 mM; 72 h;
4T1: IC50 6.7 mM, EMT6: IC50 5.6 mM, BT-549: IC50 7.3 mM, MDA-MB-231: IC50 1.8 mM
20 mg/g; 21 days; p.o.		 RTK, VEGF, EGF, IL-10, TGF-β, and CD34↓ [61]
AS-IV NRCMs, C57BL/6 40 mg/kg; 4 weeks; i.g. MDA, 8-OhdG, NOX2, and NOX4↓ [113]
DS A549,
NCI–H460, NCI–H23,
L132;
female Wistar rats		 25, 50, 100, and 200 μM; 24, 48, and 72 h;
2.5, 10 mg/kg; 28 days; i.p.		 MDA, CA 15-3, TC, TG, and HDL-C↓ [81]
AS-IV BT549,
MDA-MB-231, SPF- BALB/c nude mice		 40 mg/kg; 4 weeks; i.g. Nrf2, ARE-luciferin, BCRP, ATP, and GPx4↑ [114]
HDG Human LoVo cancer cell 1.0, 2.0, and 4.0 μM; 48 h
LoVo: IC50 1.17 μM		 Bax↑; Bcl-2 and Bcl-xL↓ [53]
Lupeol OXA-R LoVo cell 50 μM; 24 h ER stress↑; ABCG2↓ [52]
CAG SNU1,
SNU16		 50 μM; 24 h;
SNU16: IC50 5 μM		 caspase-3 and PARP cleavage↑;
p-STAT3, STAT3, JAK1, and JAK2↓		 [37]
AS-IV SD rats 10 mg/kg; 5 weeks; i.g. type I/III collagens, TGF-β, NOX2, and NOX4↓; promote
nuclear Nrf2 level.		 [115]
AS-IV C57BL/6J 20 mg/kg; 5 days/week,
6 weeks; i.g.		 SIRT1↑;
NLRP3, caspase-1/GSDMD, and caspase-3/GSDME↓		 [116]
AS-IV SD rats 40, 80 mg/kg; 1 week; i.g. NLRP3 and pro-inflammatory
cytokines↓		 [91]
HDG pTEC cells, C57BL/6J 21, 42, and 63 μM;
20, 40 mg/kg; 3 days; i.p.		 Axin2/β-catenin and
lncRNA-A330074k22Rik↓		 [117]

↓, inhibit or downregulate; ↑, activate or upregulate. IC50, half maximal inhibitory concentration; i.g., intragastrical administration; i.p., intraperitoneal injection; i.v., intravenous injection; p.o., oral administration; i.h., subcutaneous injection.