HEALTH NEWS

Study Title:

Grape Seed Extract Causes Irreparable DNA Damage to Cancer Cells

Study Abstract

Head and neck squamous cell carcinoma (HNSCC) accounts for 6% of all malignancies in United States, and unfortunately, the recurrence of secondary primary tumors and resistance against conventional treatments decrease the overall 5-year survival rate in HNSCC patients. Thus, additional approaches are needed to control HNSCC. Here, for the first time, employing human HNSCC Detroit 562 and FaDu cells as well as normal human epidermal keratinocytes (NHEK), we investigate grape seed extract (GSE) efficacy and associated-mechanism in both cell culture and nude mice xenografts. GSE selectively inhibited the growth, and caused cell cycle arrest and apoptotic death in both Detroit 562 and FaDu cells by activating DNA damage check-point cascade including ATM/ATR-Chk1/2-Cdc25C as well as caspases 8, 9 and 3. Consistent with these results, GSE treatment resulted in a strong DNA damage, and a decrease in the levels of DNA repair molecules Brca1 and Rad51 and DNA repair foci. GSE-caused accumulation of intra-cellular reactive oxygen species (ROS) was identified as a major mechanism of its effect for growth inhibition, DNA damage and apoptosis, which was remarkably reversed by antioxidant N-acetylcysteine. GSE feeding to nude mice decreased Detroit 562 and FaDu xenograft tumor growth by 67% and 65% (p<0.001), respectively. In IHC analysis, xenografts from GSE-fed groups showed decreased proliferation but increased DNA damage and apoptosis. Together, these findings show that GSE targets both DNA damage and repair, and provide mechanistic insights for its efficacy selectively against HNSCC both in cell culture and mouse xenograft; supporting its translational potential against HNSCC.

From press release:

Nearly 12,000 people will die of head and neck cancer in the United States this year and worldwide cases will exceed half a million.


A study published this week in the journal Carcinogenesis shows that in both cell lines and mouse models, grape seed extract (GSE) kills head and neck squamous cell carcinoma cells, while leaving healthy cells unharmed.

"It's a rather dramatic effect," says Rajesh Agarwal, PhD, investigator at the University of Colorado Cancer Center and professor at the Skaggs School of Pharmaceutical Sciences.

It depends in large part, says Agarwal, on a healthy cell's ability to wait out damage.

"Cancer cells are fast-growing cells," Agarwal says. "Not only that, but they are necessarily fast growing. When conditions exist in which they can't grow, they die."

Grape seed extract creates these conditions that are unfavorable to growth. Specifically, the paper shows that grape seed extract both damages cancer cells' DNA (via increased reactive oxygen species) and stops the pathways that allow repair (as seen by decreased levels of the DNA repair molecules Brca1 and Rad51 and DNA repair foci).

"Yet we saw absolutely no toxicity to the mice, themselves," Agarwal says.

Again, the grape seed extract killed the cancer cells but not the healthy cells.

"I think the whole point is that cancer cells have a lot of defective pathways and they are very vulnerable if you target those pathways. The same is not true of healthy cells," Agarwal says.

The Agarwal Lab hopes to move in the direction of clinical trials of grape seed extract, potentially as an addition to second-line therapies that target head and neck squamous cell carcinoma that has failed a first treatment.

Study Information

S. Shrotriya, G. Deep, M. Gu, M. Kaur, A. K. Jain, S. Inturi, R. Agarwal, C. Agarwal.
Generation of reactive oxygen species by grape seed extract causes irreparable DNA damage leading to G2/M arrest and apoptosis selectively in head and neck squamous cell carcinoma cells
Carcinogenesis
2012 January
University of Colorado Cancer Center and professor at the Skaggs School of Pharmaceutical Sciences.