Isoliquiritigenin induces apoptosis and cell cycle arrest through p53-dependent pathway in Hep G2 cells.
Isoliquiritigenin (ISL) is a natural pigment with the simple chalcone structure 4,2',4'-trihydroxychalcone. In this study, we report ISL induced inhibition in the proliferation of human hepatoma cells (Hep G2) for the first time. The cell proliferation inhibition achieved by ISL treatment resulted in a G2/M-phase arrest and programmed cell death. ISL treatment was found to result in the upregulation of p53, p21/WAF1, Fas/APO-1 receptor, Fas ligand, Bax and NOXA, but not in Bad. To elevate the role of p53 in these functions, we generated Hep G2 cells that express the dominant negative p53, which blocks the transcriptional activity of p53. The enhancement of p21/WAF1, Fas/APO-1, Bax and NOXA were decreased in Hep G2 cells that lack functional p53. Furthermore, Hep G2 cells were significantly more resistant to ISL when the activity of p53 was blocked. These results demonstrated that ISL-inducible p53 plays a key apoptotic role, and may do so by regulating the expression of specific target molecules that promotes efficient apoptotic cell death following G2/M-cell cycle arrest.
Hsu
Ya-Ling
YL
Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, No. 100, Shin-Chuan 1st Road, Kaohsiung 807, Taiwan.
Kuo
Po-Lin
PL
Lin
Chun-Ching
CC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002599:Chalcone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D047188:Chalcones; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D053222:Fas Ligand Protein; D022781:Hepatocytes / Q000166:cytology / Q000502:physiology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000378:metabolism
C494826:BAX protein, human; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D047188:Chalcones; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004791:Enzyme Inhibitors; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; C498702:PMAIP1 protein, human; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D002599:Chalcone; C040920:isoliquiritigenin