Differential Effects of Polyphenols on Proliferation and Apoptosis in Human Myeloid and Lymphoid Leukemia Cell Lines

Amani   A   Mahbub; Christine   L. Le   Maitre; Sarah   L.   Haywood-Small; Gordon   J.   McDougall; Neil   A.   Cross; Nicola      Jordan-Mahy

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.

Keywords: Apoptosis, cell cycle, cell proliferation, leukemia, polyphenols.

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