Journal
CANCER LETTERS
Volume 325, Issue 1, Pages 54-62Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2012.05.029
Keywords
Anthocyanidins; Lung cancer; Synergism; Apoptosis; Metastasis; Blue berry; Bilberry; Jamun
Categories
Funding
- Agnes Brown Duggan Endowment
- James Graham Brown Cancer Center funds
- Kentucky Lung Cancer Research Program
Ask authors/readers for more resources
Berry anthocyanidins (cyanidin, malvidin, peonidin, petunidin and delphinidin) have increasingly been explored for their anticancer effects; however, their combinatorial effects as a mixture, as present in blueberry, bilberry and Indian blackberry ('Jamun') remain untested. In this study, we demonstrate for the first time that the combination of suboptimal concentrations of equimolar anthocyanidins synergistically inhibited growth of two aggressive non-small-cell lung cancer cell lines, with minimal effects on non-tumorigenic cell viability. The induction of cell-cycle arrest, apoptosis and suppression of NSCLC cell invasion and migration were also significantly greater with the mixture than individual anthocyanidins. The superior effects of the combinatorial treatment presumably resulted from its effects on the oncogenic Notch and WNT pathways and their downstream targets (beta-catenin, c-myc, cyclin D1, cyclin B1, pERK, MMP9 and VEGF proteins), enhanced cleavage of the apoptotic mediators Bcl2 and PARP and enhanced inhibition of TNF alpha-induced NF-kappa B activation. In vivo, both the native mixture of anthocyanidins from bilberry (0.5 mg/mouse) and the most potent anthocyanidin, delphinidin (1.5 mg/mouse) significantly inhibited the growth of H1299 xenografts in nude mice by approximate to 60%. Notably, the effective dose of delphinidin in the anthocyanidin mixture was 8-fold lower than delphinidin alone, further emphasizing synergism. Our results thus demonstrate therapeutic potential of berries rich in this mixture of diverse anthocyanidins for non-small-cell lung cancer treatment and to prevent its future recurrence and metastasis. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available