Norsolorinic acid inhibits proliferation of T24 human bladder cancer cells by arresting the cell cycle at the G0/G1 phase and inducing a Fas/membrane-bound Fas ligand-mediated apoptotic pathway.
1. Norsolorinic acid, isolated from Aspergillus nidulans, has been shown to have antiproliferative activity in T24 human bladder cancer cells by arresting the cell cycle at the G(0)/G(1) phase and inducing apoptosis. The aim of the present study was to investigate the antiproliferative activity of norsolorinic acid in T24 human bladder cancer cells. 2. The effects of norsolorinic acid (1, 5, 10 and 20 micromol/L) on the proliferation of T24 cells and on the distribution of cells within different phases of the cell cycle were investigated indirectly using an XTT assay and a flow cytometer, respectively. Factors affecting the cell cycle and apoptosis, including p53, p21, Fas receptor, Fas ligand (FasL) and caspase 8 activity, were examined using ELISA. 3. The results showed that norsolorinic acid inhibited proliferation of T24 cells in a dose-dependent manner, with an IC(50) of 10.5 micromol/L. The effect involved the induction of cell cycle arrest at the G(0)/G(1) phase and apoptosis. 4. These results demonstrate that G(0)/G(1) phase arrest is due to increased expression of p21 in cells treated with norsolorinic acid (10 and 20 micromol/L) for 24 h. Moreover, enhanced Fas and membrane-bound Fas ligand (mFasL) may be responsible for the apoptotic effect of norsolorinic acid. Thus, the present study reports, for the first time, that induction of p21 and the Fas/mFas ligand apoptotic system may participate in the antiproliferative action of norsolorinic acid in T24 human bladder cancer cells.
Wang
Clay C C
CC
Department of Pharmacology and Pharmaceutical Science, University of Southern California, School of Pharmacy, California, USA.
Chiang
Yi-Ming
YM
Kuo
Po-Lin
PL
Chang
Jiunn-Kae
JK
Hsu
Ya-Ling
YL
D000880:Anthraquinones / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects*; D053222:Fas Ligand Protein / Q000378:metabolism* / Q000502:physiology; D016193:G1 Phase / Q000187:drug effects* / Q000502:physiology; D006131:Growth Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D016192:Resting Phase, Cell Cycle / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000517:prevention & control*; D019014:fas Receptor / Q000378:metabolism / Q000502:physiology*
D000880:Anthraquinones; D053222:Fas Ligand Protein; D006131:Growth Inhibitors; D008565:Membrane Proteins; D019014:fas Receptor; C002754:norsolorinic acid