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

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.

Glutathione is key to the synergistic enhancement of doxorubicin and etoposide by polyphenols in leukaemia cell lines

“…Five polyphenols that had been previously shown to induce apoptosis in leukaemia cells (quercetin, apigenin, emodin, rhein and cis- stilbene) 2 were combined with doxorubicin or etoposide in two lymphoid (CCRF-CEM and Jurkat) and two myeloid (THP-1 and KG1a) cell lines. These cell lines were selected as they had been identified as the most sensitive and most resistant to polyphenol-induced apoptosis; 2 in addition, two non-tumour control haemopoietic stem cells (HSCs) (CD133+ and CD34+) were investigated.…”

“…These cell lines were selected as they had been identified as the most sensitive and most resistant to polyphenol-induced apoptosis; 2 in addition, two non-tumour control haemopoietic stem cells (HSCs) (CD133+ and CD34+) were investigated.…”

ALOE EMODIN ENHANCES TAMOXIFEN CYTOTOXICITY EFFECT ON ERa-POSITIVE BREAST CANCER CELLS, MCF-7, THROUGH DOWNREGULATION OF MEK1 AND MEK2

“…The hematopoietic cells were not affected at concentrations more than 100 times higher than those required to inhibit neuroectodermal tumour cell growth (21). Lymphoid cells (JURKAT and CCRF-CEM) and the most resistant of myeloid cells (KG-1a and K562) were responsive to aloe emodin through induction of apoptosis, but not in non-tumour cells (23). Similar effects were seen with its isomer, emodin (1,3,8-trihydroxy-6-methylanthraquinone) (23).…”

“…Lymphoid cells (JURKAT and CCRF-CEM) and the most resistant of myeloid cells (KG-1a and K562) were responsive to aloe emodin through induction of apoptosis, but not in non-tumour cells (23). Similar effects were seen with its isomer, emodin (1,3,8-trihydroxy-6-methylanthraquinone) (23). Both compounds produced a synergistic effect when combined with etoposide and doxorubicin on both lymphoid cell lines (24).…”

Silencing forkhead box M1 promotes apoptosis and autophagy through SIRT7/mTOR/IGF2 pathway in gastric cancer cells

“…The principle of this method was to quantify the ATP levels and then determine the number of viable cells. 21…”