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.

Leukaemia is a malignant disease of the blood. Current treatments for leukaemia are associated with serious side-effects. Plant-derived polyphenols have been identified as potent anti-cancer agents and have been shown to work synergistically with standard chemotherapy agents in leukaemia cell lines. Polyphenols have multiple mechanisms of action and have been reported to decrease cell proliferation, arrest cell cycle and induce apoptosis via the activation of caspase (3, 8 and 9); the loss of mitochondrial membrane potential and the release of cytochrome c. Polyphenols have been shown to suppress activation of transcription factors, including NF-kB and STAT3. Furthermore, polyphenols have pro-oxidant properties, with increasing evidence that polyphenols inhibit the antioxidant activity of glutathione, causing oxidative DNA damage. Polyphenols also induce autophagy-driven cancer cell death and regulate multidrug resistance proteins, and thus may be able to reverse resistance to chemotherapy agents. This review examines the molecular mechanism of action of polyphenols and discusses their potential therapeutic targets. Here, we discuss the pharmacological properties of polyphenols, including their anti-inflammatory, antioxidant, anti-proliferative, and anti-tumour activities, and suggest that polyphenols are potent natural agents that can be useful therapeutically; and discuss why data on bioavailability, toxicity and metabolism are essential to evaluate their clinical use.

Several epidemiological studies have reported that the use of female sex steroid hormones could reduce the risk of colon cancer (CRC). This review summarizes the available data related to estradiol (E2) and progesterone (P4) single and dual treatments in CRC male and female in vitro and in vivo models, mainly from preclinical studies, alongside their potential molecular mechanisms. Most of the studies showed that E2 exogenous treatment and/or reactivation of its beta receptor (ERβ) significantly inhibited cell proliferation, induced cell cycle arrest, and promoted apoptosis by modulating several molecular pathways. Likewise, the inhibition of ERα receptors produced similar antitumorigenic actions, both in vivo and in vitro, suggesting that E2 could have dual opposing roles in CRC that are dependent on the expression profile of its nuclear receptors. The available studies on P4 are scarce, and the results revealed that in vitro and in vivo treatments with natural and synthetic progesterone were also associated with promising tumoricidal actions. Nevertheless, the combination of E2 with P4 showed enhanced anticancer activities compared with their monotherapy protocols in male–female cell lines and animals. Collectively, the studies suggested that the female sex steroid hormones could provide a novel and effective therapeutic strategy against CRC.

Polyphenols have been shown to sensitize solid tumours to alkylating agents such as cisplatin, and induce apoptosis and/or cell-cycle arrest. Here, we assess the effects of five polyphenols alone and in combination with three alkylating agents: cisplatin, cyclophosphamide and chlorambucil in lymphoid and myeloid leukaemia cells lines, and non-tumour control cells.

Dietary polyphenols influence antimetabolite agents: methotrexate, 6-mercaptopurine and 5-fluorouracil in leukemia cell lines Dietary polyphenols influence antimetabolite agents: methotrexate, 6-mercaptopurine and 5-fluorouracil in leukemia cell lines