Glycyrrhetic acid (a metabolic substance and aglycon of glycyrrhizin) induces apoptosis in human hepatoma, promyelotic leukemia and stomach cancer cells.

We have investigated the effect of glycyrrhetic acid (GR) which is metabolic substance of glycyrrhizin, on DNA of human hepatoma (HLE), promyelotic leukemia (HL-60) and stomach cancer (KATO III) cells. GR displayed apoptotic effects against HLE, HL-60 and KATO III cells. The fragmentation of DNA by GR to oligonucleosomal-sized fragments, a characteristic of apoptosis, was dose- and time-dependent in these cell lines. These findings suggest that growth inhibition of these cell lines by GR result from the induction of apoptosis by the compound. Inhibitors of caspases did not suppress the DNA fragmentation caused by GR. N-acetyl-L-cysteine, an antioxidant drug, weakly inhibited the DNA fragmentation caused by GR suggesting that active oxidants work partly as an apoptosis-inducing transfer substance.

[1]  Hidehisa Takahashi,et al.  Glycyrrhizin induces apoptosis in human stomach cancer KATO III and human promyelotic leukemia HL-60 cells. , 2005, International Journal of Molecular Medicine.

[2]  T. Kanda,et al.  Induction of apoptosis by three types of procyanidin isolated from apple (Rosaceae Malus pumila) in human stomach cancer KATO III cells. , 2004, International journal of molecular medicine.

[3]  H. Hibasami,et al.  Induction of apoptosis by lupeol isolated from mokumen (Gossampinus malabarica L. Merr) in human promyelotic leukemia HL-60 cells. , 2004, Oncology reports.

[4]  H. Hibasami,et al.  Diol- and triol-types of phytol induce apoptosis in lymphoid leukemia Molt 4B cells. , 2002, International journal of molecular medicine.

[5]  H. Hibasami,et al.  Specific induction of apoptosis by 1,8-cineole in two human leukemia cell lines, but not a in human stomach cancer cell line. , 2002, Oncology reports.

[6]  H. Hibasami,et al.  Pheophorbide a, a moiety of chlorophyll a, induces apoptosis in human lymphoid leukemia molt 4B cells. , 2000, International journal of molecular medicine.

[7]  M. Shimura,et al.  Oxidative stress as a necessary factor in room temperature‐induced apoptosis of HL‐60 cells , 2000, Journal of leukocyte biology.

[8]  H. Hibasami,et al.  Sesamin and episesamin induce apoptosis in human lymphoid leukemia Molt 4B cells. , 2000, International journal of molecular medicine.

[9]  H. Hibasami,et al.  Phytol induces programmed cell death in human lymphoid leukemia Molt 4B cells. , 1999, International journal of molecular medicine.

[10]  Ruedi Aebersold,et al.  Molecular characterization of mitochondrial apoptosis-inducing factor , 1999, Nature.

[11]  A. Uchida,et al.  Induction of apoptotic cell death in three human osteosarcoma cell lines by a polyamine synthesis inhibitor, methylglyoxal bis(cyclopentylamidinohydrazone) (MGBCP). , 1997, Anticancer research.

[12]  D. Green,et al.  The Release of Cytochrome c from Mitochondria: A Primary Site for Bcl-2 Regulation of Apoptosis , 1997, Science.

[13]  G. Kroemer,et al.  Bcl-2 inhibits the mitochondrial release of an apoptogenic protease , 1996, The Journal of experimental medicine.

[14]  J. Lotem,et al.  Cellular oxidative stress and the control of apoptosis by wild-type p53, cytotoxic compounds, and cytokines. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[15]  K. Tanaka,et al.  The genes for the alpha-type HC3 (PMSA2) and beta-type HC5 (PMSB1) subunits of human proteasomes map to chromosomes 6q27 and 7p12-p13 by fluorescence in situ hybridization. , 1995, Genomics.

[16]  H. Steller.  Mechanisms and genes of cellular suicide , 1995, Science.

[17]  S. Kaufmann.  Induction of endonucleolytic DNA cleavage in human acute myelogenous leukemia cells by etoposide, camptothecin, and other cytotoxic anticancer drugs: a cautionary note. , 1989, Cancer research.