Taraxinic Acid, a Hydrolysate of Sesquiterpene Lactone Glycoside from the Taraxacum coreanum NAKAI, Induces the Differentiation of Human Acute Promyelocytic Leukemia HL-60 Cells.

Abstract

The imbalance between cell proliferation, apoptosis and differentiation leads to the development of clones of malignant cells. Based on the understanding of tumor biology in respect to the kinetics of cell populations, two new strategies, the induction of differentiation and apoptosis, have recently emerged in the fields of cancer chemoprevention and chemotherapy. Differentiation from malignant or premalignant cells into more mature or normal-like cells, as well as apoptosis in multi-step carcinogenesis, are theoretically amenable to preventive cancer intervention. Thus, a compound with differentiation effects could be a candidate for the prevention and/or treatment of cancer. 1,2)The HL-60 cell line, derived from a patient with acute promyelocytic leukemia, provides a unique in vitro model for studying the cellular and molecular events involved in the differentiation process. Moreover, a recent approach in the treatment of leukemia includes the use of differentiation-inducing agents such as interferon, 3) retinoids, 4) and 1a,25-dihydroxyvitamin D 3 . 5,6) Based on this, the strategy of HL-60 cell differentiation has been accepted as a valid model in detecting or screening for potential cancer chemopreventive and/or chemotherapeutic agents in preclinical evaluation.Thus, as a part of our screening program to evaluate the chemopreventive potential effect of natural compounds, we have investigated the effect of taraxinic acid-1Ј-O-b-D-glucopyranoside isolated from Taraxacum coreanum NAKAI and its hydrolysate, taraxinic acid, on HL-60 growth. The whole plant of Taraxacum coreanum NAKAI has long been used for medicinal purposes due to its diuretic and anti-inflammatory activities.7) Taraxinic acid, the enzymatic hydrolysate of taraxinic acid-1Ј-O-b-D-glucopyranoside (Fig. 1) isolated from Taraxacum coreanum NAKAI, showed significant cytotoxicity, supporting that the sesquiterpene lactone is a generally active moiety. The cytotoxic effect of taraxinic acid was assessed by its differentiation-inducing activity against HL-60 cells by various biochemical examinations in the present study. Furthermore, we demonstrated that the expression of p21 CIP1 and p27 KIP1 cyclin dependant kinase inhibitor (CDKI) were increased during 48 and 72 h, whereas c-myc oncogene expression was down-regulated during the taraxinic acid-induced differentiation of HL-60 cells. This is the first report showing the mechanism of the anti-cancer effect of taraxinic acid, which may be a candidate as a differentiation-inducing cancer chemopreventive agent. MATERIALS AND METHODSMaterials P388 mouse leukemia, L-1210 mouse leukemia, SNU-C5 human colon cancer, HL-60 human promyelocytic leukemia, U-937 human histocytic lymphoma and HepG2 human hepatoma cell lines were obtained from the Korean Cell Line Bank (KCLB). RPMI 1640 medium, fetal bovine serum (FBS), penicillin, and streptomycin were obtained from Life Technologies, Inc. (Grand Island, NY, U.S.A.). b-Glycosidase, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tertazolium bromide (MTT), nitrobluetetra-...

Agrobacterium tumefaciens-mediated transformation of a medicinal plant Taraxacum platycarpum

“…Plants of the genus Taraxacum are used in herbal medicine owing to their choleretic, diuretic and anti-carcinogenic activities (Ahmad et al, 2000;Choi et al, 2002;Yun et al, 2002;Hu and Kitts, 2003). Several medicinal compounds have been isolated from the roots of these plants, including the guaianolide, desacetylmatricarin, and the germacranolides, taraxinic acid, b-glucopyranosyl ester and sonchuside A (Ho et al, 1998;Zielin´ska and Kisiel, 2000).…”

1-Chloromethyl-6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-sulfonic acid amide, a derivative of tetrahydroisoquinoline, induces granulocytic differentiation of the human leukemic HL-60 cells via G0/G1 phase arrest

“…Cell differentiation is regulated in a cell cycle-dependent manner. For instance, the differentiation of hematopoietic cells is accompanied with G0/G1 phase cell cycle arrest [18][19][20]. In this study, the cell cycle analysis revealed that CDST could markedly induce a G0/G1 phase arrest in HL-60 cells, along with a significant reduction in G2/M and S phases.…”

Taraxacum coreanum protects against glutamate-induced neurotoxicity through heme oxygenase-1 expression in mouse hippocampal HT22 cells

“…Taraxacum coreanum Nakai (Asteraceae family) is a dandelion native to Korea, and it is extensively consumed as a vegetable and used as a traditional therapeutic agent for inflammatory diseases in Korea. Previous studies of this species have revealed the presence of taraxinic acid-1'-O-β-D-glucopyranoside, of which the hydrolysate, taraxinic acid, possesses an anti-leukemic effect (10). The anti-inflammatory effect of a methanolic extract of the aerial part of T. coreanum has also been reported (11).…”