Review
Copyright ©2011 Baishideng Publishing Group Co.
World J Hepatol. Sep 27, 2011; 3(9): 228-249
Published online Sep 27, 2011. doi: 10.4254/wjh.v3.i9.228
Table 1 In vitro effects of natural terpenoids on various liver cancer cells
TerpenoidsCompoundsCellular effectsMechanismsConc.Ref.
MonoterpenesGeraniolInhibited the growth of HepG2 cells↓HMG-CoA reductase50-400 μmol/LPolo et al[68]
DiterpenesAndrographolideInhibited the growth of Hep3B cells↑apoptosis; ↑ MAPKs; ↑pJNK; ↑ERK1/23-100 μmol/LJi et al[69]
Excisanin ADecreased viability of Hep3B cells↑apoptosis; ↓pAKT1-32 μmol/LDeng et al[70]
GnidimacrinDemonstrated tumor inhibition in PKC βII-transfected HLE cells⊥G2; ↓cdc2; ↑p21WAF1/CIP10.00001-0.1 μg/mLYoshida et al[71]
OridoninPromoted cytotoxicity in HepG2 cells↑apoptosis; ↑ROS; ↑p53; ↑p38; ↓ΔΨm; ↑cyt. c; ↑caspase-3, -910-50 μmol/LHuang et al[72]
TriterpenesActeinInhibited the growth of p53-positive HepG2 cells27 μg/mL [IC50]Einbond et al[75]
Ardisiacrispin (A+B)Exhibited cytotoxicity against Bel-7402 cells↑apoptosis; ↓proliferation; microtubule disassembly1-10 μg/mLLi et al[76]
Astragaloside IVDecreased colonogenic survival and inhibited anchorage-independent growth of HepG2 cells↓Vav3.1; ↑HSP70; ↑HSPA1A; ↑HSPA8; ↑BiP/GRP78150-200 μg/mLQi et al[78]
Asiatic acidDecreased viability of HepG2 cells↑apoptosis; ↑Ca2+; ↑p5310-100 μmol/LLee et al[79]
Betulinic acidDisplayed cytotoxicity against HUH6, HepT1 and HepT3 cells↑apoptosis; ↑caspase 3; ↓PI3K/AKT; ↓GLI1; ↓PTCH1; ↓IGF21-50 μg/mLEichenmüller et al[80]
Failed to induce apoptosis against HepG2 cells↑survivin; ↑Bcl-20.1-50 μg/mLEichenmüller et al[80]
Cucurbitacin BDecreased the viability of HepG2 cells↑apoptosis; ↓Bcl-2; ↓pSTAT310 nmol/L-10 μmol/LZhang et al[83]
Exhibited growth inhibitory effects on Bel-7402 cells↑apoptosis; ⊥S; ↓cyclin D1; ↓cdc2; ↓c-Raf; ↑ERK 1/20.01-1000 μmol/LChan et al[84]
Cucurbitacin DSuppressed the growth of Hep3b cells↑apoptosis; ↑caspase-3; ↑pJNK0-10 μmol/LTakahashi et al[85]
Cucurbitacin D, IDisplayed cytotoxicity against Bel-7402 cells< 1 μmol/L [IC50]Meng et al[86]
Echinocystic acidExhibited antiproliferative effect against HepG2 cells↑apoptosis; ↓Bcl-2; ↑caspase-3, -9, -8; ↑PARP cleavage; ↓ΔΨm; ↓cyt. c; ↑p38; ↑JNK15-100 μmol/LTong et al[87]
EscinDemonstrated inhibitory effects on cell viability of HepG2 cells↑apoptosis; ⊥G1/S; ↑AIF; ↑cyt. c; ↑bax; ↓Bcl-2; ↓cyclin-E/cdk2; ↓pRb; ↓E2F10-60 μg/mLZhou et al[88]
Ganoderic acidDemonstrated an inhibition in the growth of BEL 7402 cells⊥G1/S50-500 mg/mLYang[89]
Ganoderiol FDisplayed antiproliferative effects in HepG2 , Huh7 and Hep3B cells⊥G1; ↓DNA synthesis; ↓topo I and II; ↑p16; ↓p21; ↑pERK20.1-60 μmol/LChang et al[90]
Ginsenoside-Rg1Accelerated the growth of SK-Hep-1 cells↑cyclin E; ↑cdk22.5-100 μmol/LLee et al[91]
Ginsenoside-Rg5Suppressed the growth of SK-Hep-1 cells⊥G1/S; ↓cyclin E; ↓cdk2; ↑p21WAF1/CIP1; ↓cdc25A0.1-25 μmol/LLee et al[92]
Ginsenoside Rh2Inhibited DNA synthesis in SK-Hep-1 cells⊥G1/S; ↓cyclin E; ↑p27kip1; ↓cdc25A0.25-100 μmol/LLee et al[93]
Induced cell-death in SK-Hep-1 cells↑apoptosis; ↑caspase-3; ↑PARP2-12 mg/mLPark et al[94]
Ginsenoside Rk1Inhibited the growth of HepG2 cells↑apoptosis; ↑caspase-3, -8; ↓FADD; ↓telomerase activity12.5-100 μmol/LKim et al[95]
Exhibited antiproliferative effects on HepG2 cells↑autophagy; ⊥G10-100 μmol/LKo et al[96]
Ginsenoside Rs3Displayed suppressive effects against the growth of SK-Hep-1 cells↑apoptosis; ↓cyclin E, A; ↑p53; ↑p21WAF1/CIP1; ↓cdk20.1-25 μmol/LKim et al[97]
GypenosidesExhibited cytotoxicity and decreased viability of Huh7, Hep3B and HA22T cells↑apoptosis; ↑Bax; ↑Bak; ↑Bcl-XL; ↓Bcl-2; ↓Bad; ↑cyt. c; ↑caspase-3, -9, -80.1-400 mg/mLWang et al[98]
IH-901Conferred antiproliferative effects against HepG2 cells↑apoptosis; ↑caspase-3, -8, -9; ↑PARP; ↑cyt. c10-60 μmol/LOh et al[99]
Inhibited the growth of SMMC7721 cells↑apoptosis; ⊥G0/G1; ↑Bax; ↑p53; ↑cyt. c; ↓pro-caspase-3, -95-100 μmol/LMing et al[100]
Kalopanaxsaponins A, IShowed significant cytotoxicity against HepG2 and R-HepG2 cells↑apoptosis8.9-18.1 μmol/LTian et al[101]
Keto- and acetyl-keto-boswellic acidsExhibited antiproliferative effects in HepG2 cells↑apoptosis; ⊥G1; ↑caspase-3, -8, -925-200 μmol/LLiu et al[102]
Lucidenic acid A,B,C, NDisplayed antiproliferative and anti-invasive effects against HepG2 cells↓MMP-9; ↓ERK1/2; ↓NF-κB; ↓AP-1; ↓c-Jun; ↓c-Fos10-100 μmol/LWeng et al[103,104]
LupeolExhibited growth inhibitory effects against SMMC7721 cells↑apoptosis; ↑caspase-3, -8; ↓DR3; ↑FADD6.25-200 μmol/LZhang et al[105]
25-Methoxyhispidol AShowed antiproliferative effects against SK-Hep1 cells↑apoptosis; ⊥G0/G1; ↓cyclin D1; ↓CDK4; ↓c-myc; ↓pRb; ↑p210.8-100 μmol/LHong et al[106]
Oleanolic acidDecreased the viability of HepG2, Hep3B, Huh7 and HA22T cells↑apoptosis; ↓ΔΨm; ↑caspase-3, -8; ↓Na+-K+- ATPase; ↓ICAM-1; ↓VEGF2-8 μmol/LYan et al[107]
Reduced the viability of Huh7 cells↑apoptosis; ↓ΔΨm; ↑Bax; ↓Bcl2; ↑cyt. c; ↑ caspase-3, -9; ↓NF-κB; ↓XIAP20-100 μmol/LShyu et al[108]
Ursolic acidInhibited the proliferation of HepG2 and R-HepG2 cells↑apoptosis; ⊥G1/G0; ↓COX-2; ↑HSP1053.125-100 μmol/LTian et al[109]
Suppressed the proliferation of HepG2 cells↑apoptosis; ↑p53; ↓Bcl-2; ↓survivin; ↑caspase-3; ↓PI3K/Akt5-80 μmol/LTang et al[110]
Decreased the viability of HepG2, Hep3B, Huh7 and HA22T cells↑apoptosis; ↓ΔΨm; ↑caspase-3, -8; ↓Na+-K+- ATPase; ↓ICAM-1; ↓VEGF2-8 μmol/LYan et al[107]
Reduced the viability of Huh7 cells↑apoptosis; ↓ΔΨm; ↑Bax; ↓Bcl2; ↑cyt. c; ↑ caspase-3, -9; ↓NF-κB; ↓XIAP20-100 μmol/LShyu et al[108]
WaltonitoneConferred inhibitory effects on the growth of BEL-7402 cells↑apoptosis; ↑caspase-3, -8, -9; ↑Bax; ↑cyt. c; ↑Fas; ↑FasL; ↑apaf-10.4-100 μmol/LZhang et al[111]
MiscellaneousInduced reduction in the viability of HepG2 and Hep3B cells9.4-71.1 μmol/L [IC50]Wang et al[112]
Exhibited cytotoxicity against HepG2 cells↑apoptosis; ↑p53; ⊥G1/S0.5-80 μmol/LHuang et al[113]
TetraterpenesAstaxanthin, β-CaroteneSuppressed the invasive characteristic of AH109A cellsAntioxidant mechanisms2.5-20 μmol/LKozuki et al[114]
Inhibited the migration of SK-Hep-1 cells1-20 μmol/LHuang et al[115]
Delayed the proliferation and improved the differentiation of oval cells obtained from neoplastic liver↑albumin; ↑fibrinogen; ↑hapatoglobin5 μmol/LWójcik et al[116]
Exerted genotoxic and cytotoxic effects in HepG2 cells↑apoptosis; ↑necrosis; ↑TBARS4-8 μmol/LYurtcu et al[117]
FucoxanthinInhibited the growth of HepG2 cells⊥G0/G1; ↓cyclin D1, D3; ↓cdk4; ↓pRb10-50 μmol/LDas et al[118]
Exhibited antiproliferative effect against SK-Hep-1 cells↑apoptosis; ⊥G0-G1; ↑GJIC; ↑Cx43; ↑Cx32; ↓pJNK; ↓pERK; ↑[Ca]++1-20 μmol/LLiu et al[119]
LycopeneSuppressed the invasive property of AH109A cells0.1-20 μmol/LKozuki et al[114]
Induced an inhibitory effect on the growth of Hep3b cells⊥G0/G1; DNA damage0.1-50 μmol/LPark et al[120]
Displayed antimigration and anti-invasive activity in SK-Hep-1 cells↑nm23-H11-20 μmol/LHuang et al[115]
Inhibited adhesion, invasion and migration of SK-Hep-1 cells↓MMP-9, -20.1-50 μmol/LHwang et al[121]
Inhibited SK-Hep-1 cell invasion↓MMP-9; ↓NF-κB; ↑IκBα; ↓Sp1; ↓IGF-1R; ↓ROS1-10 μmol/LHuang et al[122]
Sesquiterpenesα-BisabolbolInduced cytoxicity in HepG2 cells↑apoptosis; ↑caspase-8, -9; ↑cyt. c; ↑Bax; ↑Bak; ↓Bcl-2; ↑p53; ↑NF-κB; ↑Fas0.1-20 μmol/LChen et al[123]
DehydrocostuslactoneInhibited the proliferation of HepG2 and PLC/PRF/5 cells↑apoptosis; ↑Bax; ↑Bak; ↓Bcl-2; ↓Bcl-XL; ↑caspase-4, -9; ↑AIF; ↑Endo G; ↑ER stress; ↓CHOP/GADD153; ↑Bip; ↑MAPK; ↑pJNK; ↑ERK1/2; ↑p381-40 μmol/LHsu et al[124]
FuranodieneInhibited cell growth of HepG2 cells↑apoptosis; ⊥G2/M; altered ΔΨm; ↑cyt. c; ↑caspase-3; ↑pp38; ↓pERK1/20.1-1000 μmol/LXiao et al[125]
HOBS1, HOBS2Exhibited antiproliferative effects and induced redifferentiation in SMMC-7721 cells⊥G1; ↓AFP; ↓γ-GT; ↓TAT0.1-30 μg/mLMiao et al[126]
ZerumboneShowed antiproliferative activity against HepG2 cells↑apoptosis; ↓Bcl-2; ↑Bax3.45 μg/mL [IC50]Sakinah et al[127]