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

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:

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.

Cite this article as:

Mahbub A Amani, Maitre L. Le Christine, Haywood-Small L. Sarah, McDougall J. Gordon, Cross A. Neil and Jordan-Mahy Nicola, Differential Effects of Polyphenols on Proliferation and Apoptosis in Human Myeloid and Lymphoid Leukemia Cell Lines, Anti-Cancer Agents in Medicinal Chemistry 2013; 13 (10) . https://dx.doi.org/10.2174/18715206113139990303