Differential effects of polyphenols on proliferation and apoptosis in human myeloid and lymphoid leukemia cell lines

Anticancer Agents Med Chem. 2013 Dec;13(10):1601-13. doi: 10.2174/18715206113139990303.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Emodin / chemistry
  • Emodin / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Lymphocytes / drug effects*
  • Lymphocytes / pathology
  • Molecular Structure
  • Myeloid Cells / drug effects*
  • Myeloid Cells / pathology
  • Organ Specificity
  • Quercetin / chemistry
  • Quercetin / pharmacology*
  • Stereoisomerism
  • Stilbenes / chemistry
  • Stilbenes / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents, Phytogenic
  • Stilbenes
  • Quercetin
  • Emodin