Curcumin suppresses leukemia cell proliferation by down-regulation of P13K/AKT/mTOR signalling pathway

摘要

Purpose: To investigate the effect of curcumin ester on the proliferation of leukemia cell lines in vitro. Methods: Changes in WEHI-3 and THP 1 cell viabilities were measured using Cell Counting Kit 8 (CCK 8). Analysis of cell cycle and determination of apoptosis were carried out using propidium iodide and Annexin V fluorescein isothiocyanate staining. Transmission electron microscopy was used for observing the presence of apoptotic features in cells. Results: Treatment with curcumin ester for 72 h caused significant reduction in the proliferation of WEHI-3 and THP 1 cells. Curcumin ester, at a dose of 50 μM, decreased the proliferations of WEHI-3 and THP 1 cells to 28 and 32 %, respectively. On exposure to curcumin ester for 72 h, cell cycle in WEHI-3 cells was arrested in G1/G0 phase. Curcumin ester at doses of 25, 30 and 50 μM enhanced apoptosis in WEHI-3 cells to 46, 58 and 64 %, respectively. Curcumin ester suppressed the levels of phosphoinositide 3 kinase (PI3K), protein kinase B (AKT) and mechanistic target of rapamycin (mTOR) protein and mRNA in WEHI-3 cells. In curcumin ester-treated WEHI-3 cells, the presence of apop?totic bodies increased significantly and concentration-dependently. Conclusion: These results demonstrate that curcumin ester inhibits leukemia cell proliferation by inducing apoptosis and arresting cell cycle in G1/G0 phase, probably via suppression of PI3K, AKT and mTOR, and promotion of PTEN. Thus, curcumin ester has potentials for use in the development of an effective treatment strategy for leukemia.