Submitted to: Proceedings of the National Academy of Sciences
Publication Type: Peer reviewed journal
Publication Acceptance Date: 3/30/2006
Publication Date: 6/23/2006
Citation: Ding, M., Feng, R., Wang, S.Y., Bowman, L., Lu, Y., Qian, Y., Castranova, V., Jiang, B., Shi, X. 2006. Cyanidin-3-glucoside, a natural product derived from blackberry, exhibits chemopreventive and chemotherapeutic activity. Proceedings of the National Academy of Sciences. 281:17359-17368. Interpretive Summary: Consumption of fruits and vegetables has been associated with a lower incidence of cancer. This is because fruits and vegetables contain some substances called antioxidants. These antioxidants have been shown to reduce harmful activities of free radicals. 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 that the active ingredient in blackberries is cyanidin-3-glucoside. We isolated this compound from blackberry fruit and demonstrated that this active compound could retard tumor growth in mouse skin and reduce growth of human lung cancer cells. Our study also investigated the mechanisms of cancer inhibition by cyanidin-3-glucoside in mice. These findings demonstrate for the first time that a purified compound from blackberry fruit could inhibit tumor promoter-induced cancer growth in mice and 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 produce industry and consumers.
Technical Abstract: Epidemiological data suggest that consumption of fruits and vegetables has been associated with a lower incidence of cancer. Cyanidin-3-glucoside (C3G), a compound found in blackberry and other food products, was shown to possess chemopreventive and chemotherapeutic activity in the present study. In cultured JB6 cells, C3G was able to scavenge ultraviolet B (UVB) -induced .OH and O2.- radicals. In vivo studies indicated that C3G treatment decreased the number of nonmalignant and malignant skin tumors per mouse induced by 12-O-tetradecanolyphorbol-13-acetate (TPA) in 7, 12-dimethylbenz (a) anthracene (DMBA)-initiated mouse skin. Pretreatment of JB6 cells with C3G inhibited UVB - and TPA-induced transactivation of NF-'B and AP-1 and expression of cyclooxygenase-2 (COX-2) and tumor necrosis factor ' (TNF''. These inhibitory effects appear to be mediated through the inhibition of MAPKs activity. C3G also blocked TPA-induced neoplastic transformation in JB6 cells. In addition, C3G inhibited proliferation of a human lung carcinoma cell line, A549. Animal studies showed that C3G reduced the size of A549 tumor xenograft growth and significantly inhibited metastasis in nude mice. Mechanistic studies indicated that C3G inhibited migration and invasion of A549 tumor cells. These finding demonstrate for the first time that a purified compound of anthocyanin (C3G) inhibits tumor promoter-induced carcinogenesis and tumor metastasis in vivo.