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Shiow Wang, Kimberly Lewers, Linda Bowman, and Min Ding

Representatives of three species of strawberries (Fragaria virginiana, F. chiloensis and F. ×ananassa) were evaluated for antioxidant capacity, scavenging capacity for reactive oxygen species (ROO·, ·OH, 1O2 and O2 .-), and inhibitory effect on proliferation of A549 human lung epithelial cancer cells. Differences among the strawberry genotypes were observed for all three qualities. High antioxidant and scavenging capacities were found in `CFRA 0982', `JP 95-1-1', NC 95-19-1 and RH 30. Lowest antioxidant and scavenging capacities were found in `Allstar'. There was also a relationship between scavenging capacity and the inhibition of cancer cell proliferation. The correlations (R 2) between the scavenging capacities for the reactive oxygen species and the inhibition of cancer cell proliferation were 0.8074, 0.8279, 0.7862 and 0.7761 for ROO·, ·OH, 1O2 and O2 .-, respectively. These results suggest that antioxidants, specifically their scavenging capacities, may play an important role in the antiproliferative activity of strawberries. This study also identified strawberry germplasm of value in developing cultivars useful for cancer prevention.

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Shiow Y. Wang, Kim S. Lewers, Linda Bowman, and Min Ding

Fruit extracts from 17 to 18 representatives of three strawberry species [Fragaria virginiana Mill., F. chiloensis (L.) Mill., and F. ×ananassa Duchesne ex Rozier] were tested for the ability to inhibit proliferation of A549 human lung epithelial cancer cells. The fruit extracts also were tested for activities against free radicals, (peroxyl radicals, hydroxyl radicals, singlet oxygen, and superoxide radicals), the activities of antioxidant enzymes [glutathione peroxidase (EC 1.11.1.9), superoxide dismutase (EC 1.15.1.1), guaiacol peroxidase (EC 1.11.1.7), ascorbate peroxidase (EC 1.11.1.11), monodehydroascorbate reductase (EC 1.6.5.4), dehydroascorbate reductase (EC 1.8.5.1), and glutathione reductase (EC 1.6.4.2)], and the activities of nonenzyme antioxidant components, ascorbic acid and glutathione. Correlations between the proliferation of cancer cells and these antioxidant activities were calculated. At the species level, F. virginiana fruit extract inhibited the proliferation of A549 human lung epithelial cancer cells to a significantly greater extent (34% inhibition) than the extracts from fruit of either F. chiloensis (26%) or F. ×ananassa (25%) (P < 0.0001). Extracts from fruit of F. virginiana also had significantly greater antioxidant activities and higher activities of antioxidant enzymes and nonenzyme components than did extracts from the other two species. Among individual genotypes, there was a high positive correlation between antiproliferation of A549 cancer cells, antioxidant activities against free radicals, activities of antioxidant enzymes, and activities of nonenzyme components. Although all fruit extracts from all the strawberry genotypes inhibited proliferation of A594 cancer cells, fruit extracts from seven F. virginiana genotypes showed significantly greater antiproliferative effects than any of the F. ×ananassa or F. chiloensis genotypes. These genotypes, CFRA 0982, JP 95-1-1, NC 95-19–1, RH 30, NC 96-48-1, JP 95-9-6, and LH 50-4, may be especially useful in developing cultivars with greater anticancer potential.

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Shiow Wang, Ren-tian Feng, Linda Bowman, Ross Penhallegon, and Min Ding

The effects of lingonberry (Vaccinium vitis-idaea L.) extracts on activator protein-1 (AP-1), nuclear factor-kappaB (NF-κB), and mitogen-activated protein kinases (MAPKs) were evaluated. Pretreatment of JB6 P+ mouse epidermal cells with lingonberry extracts produced a dose-dependent inhibition of AP-1 and NF-κB induced by either 12-O-tetradecanoylphorbol-13-acetate (TPA) or ultraviolet-B (UVB) light. Lingonberry extracts blocked UVB-induced phosphorylation of MAPK family members ERK1, ERK2, and p38, but not JNK. Lingonberry extracts also prevented TPA-induced phosphorylation of ERK1 and ERK2. Results of soft agar assays indicated that lingonberry extracts suppressed TPA-induced neoplastic transformation of JB6 P+

cells in a dose-dependent manner. Lingonberry extracts also induced the apoptosis of human leukemia HL-60 cells in a dose-independent manner. These results suggest that ERK1 and ERK2 may be inhibited by lingonberries, which results in suppression of AP-1 and neoplastic transformation in JB6 P+ cells and causes cancer cell death by an apoptotic mechanism in human leukemia HL-60 cells.