Antioxidant Activities and Anti-Cancer Cell Proliferation Properties of Natsuhaze (Vaccinium oldhamii Miq.), Shashanbo (V. bracteatum Thunb.) and Blueberry Cultivars

BACKGROUND: In blueberries, the total polyphenol contents, total anthocyanin contents, and antioxidant activities of fruits in blueberries and their relatives are becoming important targets for breeders. Recently, intersectional hybrids between Japanese wild species Shashanbo and highbush blueberry were produced using polyploid breeding for the first time. However, the polyphenol contents, antioxidant activities, and anti-cancer cell proliferation properties of the fruits of these intersectional hybrids have not been studied sufficiently. OBJECTIVE: The objectives of this study were to determine the anthocyanin contents, polyphenol contents, and antioxidant activities at each stage of fruit development in intersectional hybrids, and to examine the effects of the fruit extracts on anti-cancer cell proliferation properties using human promyelocytic leukemia (HL-60) cells. METHODS: Freeze-dried fruit samples of three intersectional hybrids and their parents at five developmental stages were used to evaluate their polyphenol contents, anthocyanin contents, and levels of two types of antioxidant activities (DPPH and ORAC). The anti-cancer cell proliferation properties of each extract were also evaluated according to the survival rate of HL-60 cells. RESULTS: The total polyphenol contents in fruits of the intersectional hybrids gradually decreased as the fruits grew, but the contents increased slightly at the mature stage. Meanwhile, the total anthocyanin contents increased strongly to the mature stage. In addition, the fruit extract of intersectional hybrid JM1 was found to be more effective for inhibiting the growth of HL-60 human leukemia cells in vitro. Total polyphenol content correlated highly with antioxidant activities and anti-cancer cell proliferation properties. CONCLUSIONS: We clarified that the intersectional hybrids had produced have abundant bioactive compounds, high levels of antioxidant activities, and anti-cancer cell proliferation properties. The results proved the effectiveness of the use of Japanese wild Vaccinium species for the strategic breeding of blueberries with high levels of bioactive compounds.

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Anti-cancer activity of NVP-TAE226, a potent dual FAK/IGF-IR kinase inhibitor, against pancreatic carcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.13162 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 13162-13162 ◽

Cited By ~ 3

Author(s):

S. Hatakeyama ◽

D. Tomioka ◽

E. Kawahara ◽

N. Matsuura ◽

K. Masuya ◽

...

Keyword(s):

Cell Proliferation ◽

Pancreatic Carcinoma ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Proliferation ◽

Normal Cells ◽

P Glycoprotein ◽

Anti Cancer ◽

Cancer Activity

13162 Background: Focal adhesion kinase (FAK) is a non-receptor cytoplasmic tyrosine kinase that regulates multiple cell functions. Elevated expression levels of FAK have been detected in various tumor samples and are closely correlated with invasive potential. Activation of integrins and the growth factor receptors result in FAK autophosphorylation at Y397 and the presentation of suitable binding sites for proteins containing either SH2 or phosphotyrosine binding domains. Recent evidences suggest that FAK plays important roles in cancer cell proliferation and survival. IGF-IR function is required for tumor cell survival, but dispensable for survival of normal cells. Therefore, a dual inhibitor of both kinases may selectively block the growth, migration, and survival of FAK- and IGF-IR- expressing tumor cells compared to proliferating and migrating normal cells. Methods: In this study, anti-cancer activity of NVP-TAE226 that is identified as a potent and selective FAK inhibitor was evaluated in cancer cell lines panel and MIA PaCa-2 pancreatic carcinoma in vivo model. Results: Mean GI50 value of NVP-TAE226 against 37 cancer cell lines was 0.76 μmole/L. Inhibition of cancer cell proliferation was not affected by expression of P-glycoprotein, suggesting that NVP-TAE226 is not served as a substrate of P-glycoprotein. Oral administration of NVP-TAE226 efficiently inhibited MIA PaCa-2 human pancreatic tumor growth at all doses tested. Tumor stasis was observed at a dose of 30 mg/kg, qd for 7×/week and tumor regression was observed at a dose of 100 mg/kg, qd for 5×/week. All animals tolerated NVP-TAE226 treatment up to 100 mg/kg, 5×/wk, qd, po for 2 weeks with no body weight loss. Inhibition of downstream signaling such as phosphorylation of Akt at Serine473 was accompanied by inhibition of FAK phosphorylation in human pancreatic carcinoma cell lines. Conclusions: NVP-TAE226 is a novel class of selective and small molecule kinase inhibitors with a potent in vivo activity and potential therapeutic application. No significant financial relationships to disclose.

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