Dietary influence on pancreatic cancer growth by catechin and inositol hexaphosphate.
BACKGROUND
Pancreatic cancer is an extremely virulent form of cancer with few effective treatments. Catechin and inositol hexaphosphate (IP6), two naturally occurring molecules found in green tea and high-fiber foods, respectively, are compounds that have been shown to demonstrate anti-proliferative effects when administered as single therapeutic agents against a number of cancers. We hypothesized that, alone and in combination, IP6 and catechin would be effective against pancreatic cancer.


METHODS
Pancreatic (PANC-1 and MIAPACA) cancer cell lines were cultured and treated with IP6 (0.8 mM/well), catechin (100 microM/well), and the combination of the two. Cell viability was measured by 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide (MTT) at 24, 48, and 72 h. Vascular endothelial growth factor (VEGF) was measured in the cell supernatants by ELISA. Apoptosis was evaluated by Annexin V-fluorescein isothiocyanate (FITC).


RESULTS
The combination of catechin and IP6 significantly inhibited proliferation in the PANC-1 cell line at 24, 48, and 72 h compared to single agents (P < 0.001). Growth of the MIAPACA cell line was inhibited (P < 0.01) by each agent alone, but additive inhibitory effects were not seen. An increase in early apoptosis was attributed to catechin therapy in both cell lines (P < 0.01). The combination of these agents also increased early apoptotic activity when compared to the control (P < 0.001). IP6 reduced VEGF in both cell lines (P < 0.01). In combination, catechin and IP6 amplified VEGF reduction compared to each agent in MIAPACA and control (P < 0.002).


CONCLUSIONS
These results, combined with the prevalence of these compounds in safe, naturally occurring foods, make catechin and IP6 attractive therapies for treatment, and possibly in preventative trials, of pancreatic cancer.
McMillan
Brian
B
Department Of Surgery, Robert C. Byrd Health Science Center, West Virginia University, Morgantown, West Virginia, USA.
Riggs
Dale R
DR
Jackson
Barbara J
BJ
Cunningham
Cynthia
C
McFadden
David W
DW
D017209:Apoptosis / Q000187:drug effects; D002392:Catechin / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D009336:Necrosis; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D010833:Phytic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D013778:Tetrazolium Salts; D013844:Thiazoles; D042461:Vascular Endothelial Growth Factor A; D010833:Phytic Acid; D002392:Catechin; C022616:thiazolyl blue