Submitted to: Oncogene
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/23/2007
Publication Date: 3/14/2007
Citation: Feng, R., Wang, S.Y., Ni, H., Tourkova, I., Shulin, M., Yin, X. 2007. Cyanidin-3-rutinoside, a natural polyphenol antioxidant, selectively kills leukemic cells by induction of oxidative stress. Oncogene. 282:13468-13476 Interpretive Summary: Consumption of fruits and vegetables has been associated with a lower incidence of cancer. This is because fruits and vegetables contain substances called antioxidants. However, little is known about the active ingredients in these antioxidants and how these components exert their effects on the inhibition of cancer growth. We have identified an anticancer compound in black raspberries. We isolated this compound from black raspberry fruit and demonstrated that this active compound could reduce growth of several leukemia and lymphoma cell lines. These findings pave the way for additional investigations on the mechanisms of how fruits and vegetables promote health benefits in human. This research is helpful to other scientists and useful to the produce industry and consumers.
Technical Abstract: Anthocyanins are a group of naturally occurring phenolic compounds widely available in fruits and vegetables of human diets. They have broad biological activities including anti-mutagenesis and anti-carcinogenesis, 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 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 mitochondria pathway. Over-expression of Bcl-2 (B-cell leukemia/lymphoma 2) or Bcl-xL(B-cell leukemia/lymphoma XL) blocked caspase activation and 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 anthocyanins, such as cyanidin-3-rutinoside, could have a selective toxicity toward tumor cells, which correlates with their ability to promote oxidative stress in these cells.