Aronia melanocarpa Juice Induces a Redox-Sensitive p73-Related Caspase 3-Dependent Apoptosis in Human Leukemia Cells

Abstract

Polyphenols are natural compounds widely present in fruits and vegetables, which have antimutagenic and anticancer properties. The aim of the present study was to determine the anticancer effect of a polyphenol-rich Aronia melanocarpa juice (AMJ) containing 7.15 g/L of polyphenols in the acute lymphoblastic leukemia Jurkat cell line, and, if so, to clarify the underlying mechanism and to identify the active polyphenols involved. AMJ inhibited cell proliferation, which was associated with cell cycle arrest in G2/M phase, and caused the induction of apoptosis. These effects were associated with an upregulation of the expression of tumor suppressor p73 and active caspase 3, and a downregulation of the expression of cyclin B1 and the epigenetic integrator UHRF1. AMJ significantly increased the formation of reactive oxygen species (ROS), decreased the mitochondrial membrane potential and caused the release of cytochrome c into the cytoplasm. Treatment with intracellular ROS scavengers prevented the AMJ-induced apoptosis and upregulation of the expression of p73 and active caspase 3. The fractionation of the AMJ and the use of identified isolated compounds indicated that the anticancer activity was associated predominantly with chlorogenic acids, some cyanidin glycosides, and derivatives of quercetin. AMJ treatment also induced apoptosis of different human lymphoblastic leukemia cells (HSB-2, Molt-4 and CCRF-CEM). In addition, AMJ exerted a strong pro-apoptotic effect in human primary lymphoblastic leukemia cells but not in human normal primary T-lymphocytes. Thus, the present findings indicate that AMJ exhibits strong anticancer activity through a redox-sensitive mechanism in the p53-deficient Jurkat cells and that this effect involves several types of polyphenols. They further suggest that AMJ has chemotherapeutic properties against acute lymphoblastic leukemia by selectively targeting lymphoblast-derived tumor cells.

Extracts of Strawberry Fruits Induce Intrinsic Pathway of Apoptosis in Breast Cancer Cells and Inhibits Tumor Progression in Mice

“…These results suggest that activation of p73, when p53 is mutated, is a good strategy to induce apoptosis in cancer cells. Previously, studies using polyphenolic rich Aronia melanocarpa juice also showed activation of p73 in p53 null cells [38]. Besides, it has been shown that polyphenols isolated from red vines, known as gallic acid can inhibit the induction and progression of colon cancer in mice models [39].…”

Evasion of anti-growth signaling: A key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds

“…Upregulation of p73 was reported in response to EGCG in multiple myeloma cells [255]. Polyphenol-rich Aronia melanocarpa juice induces cell cycle arrest and apoptosis by redox sensitive activation of p73 [256]. …”

Selective ROS-dependent p53-associated anticancer effects of the hypoxoside derivative rooperol on human teratocarcinomal cancer stem-like cells

“…Rooperol induced a ROS-dependent, p53-and caspase-3-associated apoptosis in cancer stem-like cells Recent findings indicated that phenolic compounds can induce ROS-dependent apoptosis in cancer cells [20,22] by producing either superoxide anions or hydrogen peroxide. To determine whether a ROS-signaling pathway could be involved in rooperol-induced apoptosis and additionally to determine the implicated sources of ROS, we examined the effects of various antioxidants on rooperol-treated NT2/D1 teratocarcinomal stem-like cells.…”

“…The levels of cellular ROS production were determined as previously described [20]. Briefly, cells seeded at an initial density of 2×10 6 cells/well in 6-well plates, were exposed for 2 h to either vehicle or increasing concentrations of rooperol and then stained for 15 min at room temperature with a 1 μM dihydroethidine (DHE) solution; DHE is a redox-sensitive fluorescent probe which is rapidly oxidized by superoxide anions, resulting in red fluorescent ethidium which accumulates in the nucleus by intercalating into DNA.…”