UAB finds grape extract that kills lung cancer cells

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I've been taking good quality proanthocyanidins for years ....

UAB finds grape extract that kills lung cancer cells

By Paul Hamaker, Birmingham Science News Examiner

..Researchers at the University of Alabama at Birmingham and the Birmingham Veterans Affairs Medical Center announced the discovery of the effective use of grape seed proanthocyanidins to produce cancer cell death in lung cancer at the Public Library of Science web site on November 8, 2011.

"If, the body weight of a normal standard person is considered to be 70 Kg, then 1.13 g GSPs will be required for a healthy person/day to produce same level of anti-lung carcinogenic effects as observed in mice, which seems reasonable, affordable and attainable.

In summary, the novelty of this study lies in the analysis of chemotherapeutic effects of GSPs on additional new molecular targets of NSCLC cells using both in vitro and in vivo models. This detailed and systematic study revealed that GSPs induce apoptosis of human non-small cell lung cancer cells by loss of mitochondrial membrane potential, which was not reported earlier in this model. The present findings provide pre-clinical data suggesting that grape seed proanthocyanidins have the potential to be developed as a pharmacologically safe agent either alone or in combination with other drugs for the treatment of non-small cell lung cancers in humans."

Lung cancer remains the leading cause of cancer-related deaths worldwide, and non-small cell lung cancer (NSCLC) represents approximately 80% of total lung cancer cases. The use of non-toxic dietary phytochemicals can be considered as a chemotherapeutic strategy for the management of the NSCLC. Here, we report that grape seed proanthocyanidins (GSPs) induce apoptosis of NSCLC cells, A549 and H1299, in vitro which is mediated through increased expression of pro-apoptotic protein Bax, decreased expression of anti-apoptotic proteins Bcl2 and Bcl-xl, disruption of mitochondrial membrane potential, and activation of caspases 9, 3 and poly (ADP-ribose) polymerase (PARP). Pre-treatment of A549 and H1299 cells with the caspase-3 inhibitor (z-DEVD-fmk) significantly blocked the GSPs-induced apoptosis of these cells confirmed that GSPs-induced apoptosis is mediated through activation of caspases-3. Treatments of A549 and H1299 cells with GSPs resulted in an increase in G1 arrest. G0/G1 phase of the cell cycle is known to be controlled by cyclin dependent kinases (Cdk), cyclin-dependent kinase inhibitors (Cdki) and cyclins. Our western blot analyses showed that GSPs-induced G1 cell cycle arrest was mediated through the increased expression of Cdki proteins (Cip1/p21 and Kip1/p27), and a simultaneous decrease in the levels of Cdk2, Cdk4, Cdk6 and cyclins. Further, administration of 50, 100 or 200 mg GSPs/kg body weight of mice by oral gavage (5 d/week) markedly inhibited the growth of s.c. A549 and H1299 lung tumor xenografts in athymic nude mice, which was associated with the induction of apoptotic cell death, increased expression of Bax, reduced expression of anti-apoptotic proteins and activation of caspase-3 in tumor xenograft cells. Based on the data obtained in animal study, human equivalent dose of GSPs was calculated, which seems affordable and attainable. Together, these results suggest that GSPs may represent a potential therapeutic agent for the non-small cell lung cancer.

Paper

Grape Proanthocyanidins Induce Apoptosis by Loss of Mitochondrial Membrane Potential of Human Non-Small Cell Lung Cancer Cells In Vitro and In Vivo

Authors

Tripti Singh2, Som D. Sharma2, Santosh K. Katiyar1,2,3,4*

1 Birmingham Veterans Affairs Medical Center, Birmingham, Alabama, United States of America, 2 Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, 3 Nutrition Obesity Research Center, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, 4 Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama, United States of America

Citation: Singh T, Sharma SD, Katiyar SK (2011) Grape Proanthocyanidins Induce Apoptosis by Loss of Mitochondrial Membrane Potential of Human Non-Small Cell Lung Cancer Cells In Vitro and In Vivo. PLoS ONE 6(11): e27444. doi:10.1371/journal.pone.0027444

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