Title:Differential Effects of Polyphenols on Proliferation and Apoptosis in Human Myeloid and Lymphoid Leukemia Cell Lines
VOLUME: 13 ISSUE: 10
Author(s):Amani A Mahbub, Christine L. Le Maitre, Sarah L. Haywood-Small, Gordon J. McDougall, Neil A. Cross and Nicola Jordan-Mahy
Affiliation:Sheffield Hallam University, Faculty of Health and Wellbeing, Sheffield, UK.
Keywords:Apoptosis, cell cycle, cell proliferation, leukemia, polyphenols.
Abstract:Background: Mortality rates for leukemia are high despite considerable improvements in treatment. Since polyphenols exert
pro-apoptotic effects in solid tumors, our study investigated the effects of polyphenols in haematological malignancies. The effect of
eight polyphenols (quercetin, chrysin, apigenin, emodin, aloe-emodin, rhein, cis-stilbene and trans-stilbene) were studied on cell
proliferation, cell cycle and apoptosis in four lymphoid and four myeloid leukemic cells lines, together with normal haematopoietic
control cells.
Methods: Cellular proliferation was measured by CellTiter-Glo® luminescent assay; and cell cycle arrest was assessed using flow
cytometry of propidium iodide stained cells. Apoptosis was investigated by caspase-3 activity assay using flow cytometry and apoptotic
morphology was confirmed by Hoescht 33342 staining.
Results: Emodin, quercetin, and cis-stilbene were the most effective polyphenols at decreasing cell viability (IC50 values of 5-22 μM,
8-33 μM, and 25-85 μM respectively) and inducing apoptosis (AP50 values (the concentration which 50% of cells undergo apoptosis) of
2-27 μM, 19-50 μM, and 8-50 μM respectively). Generally, lymphoid cell lines were more sensitive to polyphenol treatment compared to
myeloid cell lines, however the most resistant myeloid (KG-1a and K562) cell lines were still found to respond to emodin and quercetin
treatment at low micromolar levels. Non-tumor cells were less sensitive to all polyphenols compared to the leukemia cells.
Conclusions: These findings suggest that polyphenols have anti-tumor activity against leukemia cells with differential effects.
Importantly, the differential sensitivity of emodin, quercetin, and cis-stilbene between leukemia and normal cells suggests that
polyphenols are potential therapeutic agents for leukemia.
