Black raspberry components inhibit proliferation, induce apoptosis, and modulate gene expression in rat esophageal epithelial cells. Nutr Cancer 2009;61(6):816-26
Date
02/16/2010Pubmed ID
20155622Pubmed Central ID
PMC3015087DOI
10.1080/01635580903285148Scopus ID
2-s2.0-77952533840 (requires institutional sign-in at Scopus site) 81 CitationsAbstract
We have shown that a diet containing freeze-dried black raspberries (BRB) inhibits the development of chemically induced cancer in the rat esophagus. To provide insights into possible mechanisms by which BRB inhibit esophageal carcinogenesis, we evaluated an ethanol (EtOH) extract of BRB, and two component anthocyanins (cyanidin-3-O-glucoside and cyanidin-3-O-rutinoside) in BRB, for their effects on growth, apoptosis, and gene expression in rat esophageal epithelial cell lines. The EtOH extract and both anthocyanins selectively caused significant growth inhibition and induction of apoptosis in a highly tumorigenic cell line (RE-149 DHD) but not in a weakly tumorigenic line (RE-149). The uptake of anthocyanins from the EtOH extract into RE-149 DHD cells far exceeded their uptake into RE-149 cells, which may have accounted for the selective effects of the extract on growth and apoptosis of RE-149 DHD cells. The growth inhibitory and proapoptotic effects were enhanced by the daily addition of the EtOH extract and the anthocyanins to the medium. Interestingly, the EtOH extract did not alter cyclooxygenase-2 (COX-2) and nitric oxide synthase (i-NOS) expression in RE-149 DHD cells, whereas both anthocyanins downregulated the expressions of these genes. This differential effect may have been related to the relative amounts of anthocyanins in the extract vs. when they were added individually to the medium. We conclude that the selective effects of the EtOH extract on growth and apoptosis of highly tumorigenic rat esophageal epithelial cells in vitro may be due to preferential uptake and retention of its component anthocyanins, and this may also be responsible for the greater inhibitory effects of freeze-dried whole berries on tumor cells in vivo.
Author List
Zikri NN, Riedl KM, Wang LS, Lechner J, Schwartz SJ, Stoner GDMESH terms used to index this publication - Major topics in bold
AnimalsAnimals, Newborn
Anthocyanins
Antineoplastic Agents, Phytogenic
Apoptosis
Caspases, Effector
Cell Line, Tumor
Cell Proliferation
Cell Transformation, Neoplastic
Cyclooxygenase 2
Dose-Response Relationship, Drug
Epithelial Cells
Esophageal Neoplasms
Fruit
Gene Expression Regulation, Neoplastic
Glucosides
Neoplasm Transplantation
Nitric Oxide Synthase Type II
Phytotherapy
Plant Extracts
Rats
Rats, Inbred F344
Rosaceae
Time Factors
Tumor Burden