Effects of water garlic extracts on cell cycle and viability of HepG2 hepatoma cells.
Garlic extracts, either aqueous or oily, are commonly employed to prepare garlic derivative supplements used as nutraceuticals for the treatment of different pathologies. In this study, we investigated the effects of water garlic extracts from two different areas of Italy well known for garlic production, Latina (GEL) and Sulmona (GES), on cell cycle and death of HepG2 hepatoma cells. The effects of the treatments with GEL and GES were also compared with the oil-soluble sulfur compound of garlic, diallyl disulfide (DADS). GEL and GES induced a p53/p21-dependent cell cycle arrest in G2/M phase and apoptosis, although to a different extent, whereas DADS, under the experimental conditions used, was not detrimental to HepG2 cells. GEL and GES committed HepG2 cells to apoptosis by the activation of c-Jun-NH(2) terminal kinase (JNK)/c-Jun phosphorylative cascade without a detectable increase in the flux of reactive oxygen species. Moreover, differentiation of HepG2 cells induced by retinoic acid determined resistance to GEL and GES treatments without the activation of JNK signaling pathway. Overall, the results obtained indicate that water-soluble garlic extracts are more inhibitory of the growth of transformed hepatoma cells than the oil-soluble isolated compound DADS, and that their antiproliferative properties are different depending on the area of origin of the starting material.
De Martino
Angelo
A
Department of Biology, University of Rome "Tor Vergata," Via della Ricerca Scientifica, 00133 Rome, Italy. demartino@bio.uniroma2.it
Filomeni
Giuseppe
G
Aquilano
Katia
K
Ciriolo
Maria R
MR
Rotilio
Giuseppe
G
D000498:Allyl Compounds / Q000494:pharmacology; D015415:Biomarkers; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004220:Disulfides / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005737:Garlic / Q000737:chemistry*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D012643:Selenium / Q000737:chemistry; D015398:Signal Transduction; D014212:Tretinoin / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014867:Water
D000498:Allyl Compounds; D015415:Biomarkers; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004220:Disulfides; D010936:Plant Extracts; D016159:Tumor Suppressor Protein p53; D014867:Water; D014212:Tretinoin; C028009:diallyl disulfide; D048031:JNK Mitogen-Activated Protein Kinases; D012643:Selenium