Copyright ©The Author(s) 2022.
World J Gastroenterol. Jul 28, 2022; 28(28): 3535-3554
Published online Jul 28, 2022. doi: 10.3748/wjg.v28.i28.3535
Table 1 Various synthetic and natural peroxisome-proliferator-activated receptor gamma agonist used in experimental and clinical trials for hepatocellular carcinoma
Agonist name
Drug bank/ PubChem ID
Concentration/dose of agonist
Synthetic agonists
PioglitazoneDB01132In vivo (Rats, and Mice)3 mg/kg; 10 mg/kgReduced HCC progression and decreased tumor size and volume[44]
RosiglitazoneDB00412In vivo (Orthotopic Mice)In vitro (MHCC97L, and BEL-7404)50 µmol/LDecreased HCC migration, and invasiveness[25]
In vitro (HepG2 and PC3)0.1, 1, 10, 100 µmol/LReduced cancer growth, Increased apoptosis[49]
In vitro (HepG2 and Hep3B)80 µmol/LRestricted the oncogenic activity of SEPT2[50]
TelmisartanDB00966In vitro (HLF, HLE, HuH-7, PLC/PRF/5, and HepG2)10, 50 or 100 µmol/LInhibit proliferation, induce cell cycle arrest[53]
In vivo (Mice)15 mg/kgReversed malignant anomalies, antioxidant, anti-inflammatory[54]
TroglitazoneDB00197In vitro (Hep G2, HuH-7, KYN-1, and KYN-2)5, 10, 25 µmol/LReduced cell proliferation and increased apoptosis[56]
In vitro (HepG2)5, 10, 20, 40, 80, and 100 µmol/LApoptosis and growth inhibition[57]
In vitro (Hep G2, HuH-7, KYN-1, and KYN-2)5, 10, and 25 µmol/LInhibited DNA synthesis, cell cycle growth, and α-fetoprotein levels[58]
In vitro (PLC/PRF/5, and HuH-7)5, 10, 20, 40, 60, 80, and 100 µmol/LReduced cell proliferation and increased apoptosis[59]
In vitro (HLF, HAK-1A, HAK-1B, and HAK-5)10, 20, 30, 40, and 50 µmol/LReduced cell proliferation and increased apoptosis[19]
SaroglitazarDB13115In vivo (Mice)4 mg/kgReduced inflammation in hepatic lobules, hepatocellular ballooning, and steatosis[61]
In vivo (Rats)4 mg/kgImproved lipid profile, and histopathological changes[62]
Natural agonists
Cannabinol, CannabinoidsDB14737In vitro (HepG2 and HUH-7); In vivo (Mice)8 µmol/L; 15 mg/kgIncreased apoptosis, autophagy, anti-proliferative[66]
In vitro (HEK-293T and Neuro-2a); In vivo (Mice)1, 5, 10, 25 µmol/L; 20 mg/kgAntitumor, antioxidant, anti-inflammatory[68]
CapsaicinDB06774In vivo (Rats)0.5 and 1 mg/kgInhibit hepatic injury, and collagen deposition, anti-inflammatory[71]
CurcuminDB11672In vivo (Rats)20 mg/kg Attenuated histopathological, serological, proliferative, and apoptotic parameters[77]
In vitro (H22); In vivo (Mice)5, 10, 20, 40, and 80 µmol/L; 50, 100 mg/kgAntiproliferative, decrease tumor growth, induce apoptosis[78]
In vivo (Mice)150 mg/kgReduced inflammation, and tumor size[79]
In vivo (Rats)0.5, 1, 2, 5, 10, 15, and 20 ng/mLInterrupted TGFβ signaling, activated hepatic stellate cells[80]
In vitro (SMMC7721 and Huh-7)10, 20, 40, 80, and 160 µmol/LSuppressed cellular proliferation[82]
HesperidinDB04703In vivo (Rats)50 and 100 mg/kgSuppressed TGFβ signaling and hepatocarcinogenesis[85]
In vivo (Rats)200 mg/kgInhibited PI3K/Akt pathway, Antioxidant[86]
In vitro (HepG2); In vivo (Rats)100 µmol/L; 150 mg/kgInhibited Wnt3a/5a signaling pathway, anti-inflammatory[87]
HispidulinDB14008In vitro (SMMC7721 and Bel7402); In vivo (mouse tumor xenograft)10 and 20 µmol/L; 20 and 40 mg /kgAnticancerous, inhibited cell migration[89]
In vitro (NCI-H460 and A549)4, 8, 15, 30, and 60 µmol/LInduced ROS-mediated apoptosis, anti-cancerous[90]
IsoflavoneDB12007In vivo (Bel-7402 and SK-Hep-1)In vivo (Mice)75 and 12 µmol/L resp.; 25 and 7.5 mg/kg resp.Anti-inflammatory, anti-tumorigenic, reduced the size and volume of tumor[94]
In vitro (Hepa 1-6 cells)1, 5, 10, 15, 20, 25, 50, 75, and 100 μmol/LAntitumorigenic and antiproliferative[95]
In vitro (HCC-LM3, SMMC-7721, Hep3B, Bel-7402, and Huh-7)In vivo (Mice)40, 60, and 80 μmol/L; 20, 40, and 80 mg/kgSuppressed aerobic glycolysis and increased apoptotic rate[96]
Oroxyloside14655551In vitro (HepG2) and SMMC-7721); In vivo (Mice)100, 200, and 300 μmol/L; 90 mg/kgCell cycle arrest and growth repression[100]
ResveratrolDB02709In vivo (Rats)100 mg/kgAntioxidant, anti-inflammatory, anticancer[101]
In vitro (HepG2); In vivo (Rats)7.81, 15.63, 31.25, 62.5, 125, and 250 µg/mL; 20 mg/kgAttenuated histopathological, serological, proliferative, and apoptotic parameters[102]
Avicularin5490064In vitro (HuH-7)25, 50, and 100 µg/mLDecreased the cell migration and invasiveness[107]
Honokiol72303In vitro (HEK-293 and 3T3-L1); In vivo (Mice)1, 3, and 10 μmol/L; 100 mg/kgActivated PPARγ/RXR heterodimers; Reduced hyperglycemia[108]
ChrysinDB15581In vitro (MDA-MB-231 and HepG2)In vivo (Mice)10 µmol/L; 10 mg/kgIncreased apoptosis[112]
QuercetinDB04216In vitro (HepG2 and SMCC-7721); In vivo (Mice)0.05, 0.1, and 0.15 mmol/L; 40 mg/kgPromoted the autophagy[114]
In vitro (PATU-8988 and PANC-1)20, 40, 80, and 160 µmol/LSuppressed HCC via STAT3 pathway[117]
In vitro (LM3); In vivo (Mice)40, 80, and 120 µmol/L; 100 mg/kgReduced invasiveness, Cell cycle regulation[118]
Clinical trials
Population typeNo. of patients
ThiazolidinedionesNAHongkong1153Reduce the synergistic effect of diabetes with liver disorders; Reduced risk of HCC[38],[39],[40],[41]
PioglitazoneDB01132Chinese75Blocked RAGE signaling; Reduced HCC[45]
Japanese85Reduced growth and invasion of HCC cells[46]
Thai10000Reduced risk of HCC[47]
RosiglitazoneDB00412French44Reduced NASH activity and ballooning score, Ameliorated histopathological aberrations[51]
SaroglitazarDB13115Indian30 Improved glycemic index and liver stiffness[63]
90 Improved fibrosis score[64]
IsoflavoneDB12007Japanese302Antioxidant, reduced risk of HCC[97]
191Antioxidant, reduced risk of HCC[98]