title: Growth inhibition of luteolin on HepG2 cells is induced via p53 and Fas/Fas-ligand besides the TGF-β pathway.
abstract: Flavonoids, a class of natural polyphenolic compounds, inhibit cell cycle progression and induce apoptosis. This study was performed to investigate the antiproliferative effect of luteolin, the flavonoid isolated from Ixeris sonchifolia Hance, and to elucidate the detailed apoptotic mechanism in HCC cells. According to the result of MTT assay luteolin possessed antiproliferative effect, and HepG2 cells were the most sensitive to luteolin. Propidium iodide staining, fluorescence activated cell sorting analysis, western blot analysis and RT-PCR were applied to compare the difference of apoptotic event between the two HCC cell lines, with wild-type p53 (HepG2) or not (Hep3B) based on time and concentration. The treatment of luteolin upregulated the expression levels of transforming growth factor β1 (TGF‑β1), p21WAF1/CIP1, p27KIP1, Smad4, and Fas in HCC cells. Thus, the expression of p21WAF1/CIP1 was controlled by another factor, such as TGF‑β1 in addition to p53, and notably the key factor might be p21WAF1/CIP1 in the remarkable switch to G1 cell cycle arrest in HepG2 cells rather than p27KIP1. Luteolin induced apoptotic cell death in Hep3B cells while caused G1 arrest in HepG2 cells. Taken together, we conclude that luteolin induces apoptosis from G1 arrest via three signaling pathways of TGF‑β1, p53, and Fas/Fas-ligand in HCC cells.
authors.affiliation: Department of Clinical Laboratory Science, College of Nursing and Healthcare Sciences, Dong-Eui University, Busan 614-714, Republic of Korea.
authors.forename: Su Bog
authors.initials: SB
authors.lastname: Yee
authors.affiliation: Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Hye Joung
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Sang Woon
authors.initials: SW
authors.lastname: Chung
authors.affiliation: School of Medicine, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Dong Heun
authors.initials: DH
authors.lastname: Park
authors.affiliation: Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Bokyung
authors.initials: B
authors.lastname: Sung
authors.affiliation: Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
authors.affiliation: Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Nam Deuk
authors.initials: ND
authors.lastname: Kim
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D049109:Cell Proliferation / Q000187:drug effects; D053222:Fas Ligand Protein / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D047311:Luteolin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics* / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C495901:TP53 protein, human; D016212:Transforming Growth Factor beta; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor; D047311:Luteolin