ISHS Acta Horticulturae 786: International Workshop on Medicinal and Aromatic Plants
THE EFFECT OF MEK AND PI3-K INHIBITORS ON HL-60 CELL APOPTOSIS INDUCED BY THE EXTRACTS OF ALPINIA GALANGA |
| Authors: | R. Banjerdpongchai, P. Kongtawelert, W. Pompimon |
| Keywords: | leukemic cells, mitogen-activated ERK-activating kinase, phosphatidylinositol-3 kinase, hexane extract, programmed cell death |
| Abstract:
Alpinia galangal, or 'Kha' in Thai, is a plant from which rhizomes are used in cooking. It is in the family of Zingiberaceae. The aims of this study were to evaluate the apoptotic effects of A. galanga hexane extracts, MEK and phosphatidylinositol-3 kinase (PI3-K) inhibitors on human promyelocytic leukemic (HL-60) cells. It was found that hexane extract of A. galanga induced HL-60 cell apoptosis in a dose-dependent manner. Further investigation of this material by fractionation using silica gel chromatography obtained KF4, or Kha fraction 4, and it induced HL-60 cells to undergo apoptosis in a concentration-dependent manner, whereas KF1 or fraction 1, 10 mg/ml, induced apoptosis maximally and minimally at 100 mg/ml. The morphology of cells treated with KF1 and KF4 was condensed nuclei and apoptotic bodies under fluorescence microscope, and the DNA of the cells treated with KF4 showed ladder pattern on agarose gel electrophoresis. KF2 and KF3 did not induce apoptosis. Wortmannin, a phosphatidylinositol 3-kinase inhibitor, enhanced the apoptotic effect of KF4 (20 mg/ml) on HL-60 cells dose-dependently. U0126 (a MEK-1 and MEK-2 inhibitor) by itself is cytotoxic to HL-60 cells, i.e., it caused apoptosis at 10, 20, and 50 mM, and when combined with KF4 (20 mg/ml) it enhanced the number of apoptotic cells at U0126 concentrations of 10 and 20 mM. PD98059 (a MAPKK or MEK inhibitor) at the doses of 10, 20, and 50 mM increased the apoptotic cells when induced with KF4 at 20 mg/ml. HL-60 cells which were treated with KF1 or KF4 underwent apoptosis through caspase-3-dependent pathway. KF4 at 20 mg/ml also accelerated the apoptotic effect of paclitaxel, which is a chemotherapeutic drug (at 10 mM). Hence, extracts of A. galangal, MEK and PI3-K inhibitors may be of clinical use for leukemic patients and in vivo study is required before further implication. | |
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