Cyanidin-3-rutinoside, a Natural Polyphenol Antioxidant, Selectively Kills Leukemic Cells by Induction of Oxidative Stress

Abstract

Anthocyanins are a group of naturally occurring phenolic compounds widely available in fruits and vegetables in human diets. They have broad biological activities including antimutagenesis and anticarcinogenesis, which are generally attributed to their antioxidant activities. We studied the effects and the mechanisms of the most common type of anthocyanins, cyanidin-3-rutinoside, in several leukemia and lymphoma cell lines. We found that cyanidin-3-rutinoside extracted and purified from the black raspberry cultivar Jewel induced apoptosis in HL-60 cells in a dose-and time-dependent manner. Paradoxically, this compound induced the accumulation of peroxides, which are involved in the induction of apoptosis in HL-60 cells. In addition, cyanidin-3-rutinoside treatment resulted in reactive oxygen species (ROS)-dependent activation of p38 MAPK and JNK, which contributed to cell death by activating the mitochondrial pathway mediated by Bim. Down-regulation of Bim or overexpression of Bcl-2 or Bcl-x L considerably blocked apoptosis. Notably, cyanidin-3-rutinoside treatment did not lead to increased ROS accumulation in normal human peripheral blood mononuclear cells and had no cytotoxic effects on these cells. These results indicate that cyanidin-3-rutinoside has the potential to be used in leukemia therapy with the advantages of being widely available and selective against tumors.

Autophagy inhibition enhances anthocyanin-induced apoptosis in hepatocellular carcinoma

“…On the other hand, they contribute to the antiproliferative activity of vegetables and fruits, including berries, by inducing the apoptosis of cancer cells (29, 30, 34 -37). Despite their antioxidant action, paradoxically, they exhibit pro-oxidant activity resulting in selective cell death of leukemia cells (37).…”

Cancer chemoprevention and chemotherapy: Dietary polyphenols and signalling pathways

“…Similarly, anthocyanins also induced ROS-dependent activation of p38 and JNK, which contributed to the apoptotic effect in leukaemia cells [89].…”

“…Anthocyanins induced apoptosis in colon cancer cells, since DNA fragmentation and unbalance between Bax and Bcl-2 mRNA expressions were observed [82]. Moreover, anthocyanins activated the mitochondrial pathway through Bim, by increasing ROS generation in leukaemia cells, but not in normal human peripheral blood mononuclear cells [89]. Similarly, galangin, a flavonol present in India root spice and propolis, exerted an antiproliferative effect on leukaemia, which was associated to apoptosis induction as it was demonstrated by detected DNA fragmentation, increased hypodiploid peak of DNA content and enhanced expression of active caspase-3, although increased ROS generation was not reported [99].…”

Antioxidant Activities of Chokeberry Extracts and the Cytotoxic Action of Their Anthocyanin Fraction on HeLa Human Cervical Tumor Cells

“…Similar observations were reported in a recent study of cyanidin 3-rutinoside, an anthocyanin extracted and purified from black raspberry, administered to HL-60 leukemic cells, which determined the increase of ROS in human leukemia cells, but the ROS accumulation decreased with time. 46 A dose-dependent increase of intracellular ROS level was observed when the cells were treated with 25-125 lM delphinidin 3-sambubioside obtained from the dried flower of Hibiscus sabdariffa. 47 Also, oxidative stress-induced ROS production was observed in HepG2 cells treated with an anthocyaninrich extract from Thai black sticky rice.…”