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J. Biol. Chem., Vol. 281, Issue 25, 17359-17368, June 23, 2006

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Cyanidin-3-glucoside, a Natural Product Derived from Blackberry, Exhibits Chemopreventive and Chemotherapeutic Activity^*

Min Ding¹, Rentian Feng, Shiow Y. Wang, Linda Bowman, Yongju Lu, Yong Qian, Vincent Castranova, Bing-Hua Jiang^¶, and Xianglin Shi

From the Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, the Fruit Laboratory, Beltsville Agricultural Research Center, U. S. Department of Agriculture, Beltsville, Maryland 20705, and the ^¶Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, West Virginia 26505

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-induced ·OH and radicals. In vivo studies indicated that C3G treatment decreased the number of non-malignant and malignant skin tumors per mouse induced by 12-O-tetradecanolyphorbol-13-acetate (TPA) in 7,12-dimethylbenz[a]anthracene-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 and tumor necrosis factor-. These inhibitory effects appear to be mediated through the inhibition of MAPK 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 inhibits tumor promoter-induced carcinogenesis and tumor metastasis in vivo.

Received for publication, January 27, 2006 , and in revised form, March 30, 2006.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Pathology and Physiology Research Branch, Health Effect Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505. Tel.: 304-285-6229; Fax: 304-285-5938; E-mail: mid5{at}cdc.gov.

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