A pyrolytic compound of curcumin, a dietary deketene curcumin to inhibit gastric carcinogenesis in a mouse model.

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e15518 Background: Gastric cancer is the second cause of cancer death in the world, killing more than 700,000 people in 2012. The risk factors are Helicobacter pyloriinfection, obesity, smoking, consumption of red meat or alcohol. However, an effective preventive measure of this disease has bot been established. Curcumin, a dietary pigment, that has been used for more than three thousand years, has an anti-tumor potential. However, bioavailability of curcumin is very poor, and it is not used in clinics. Researchers are trying to overcome this short point. To synthesize a new analog bearing higher anti-tumor potential is our solution, and we have successfully developed a series of new diarylpentanoid analogs. Our diarylpentanoid analogs are structurally different from curcumin, a diarylheptanoid. Recently, a breakthrough finding that a deketene curcumin is formed as a result of pyrolysis of curcumin during cooking of curry, was published. This deketene curcumin is identical to one of our analogs, 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one, named GO-Y022. For this reason, we investigate the efficacy and safety issues of GO-Y022 in a mouse gastric cancer model. Methods: We assessed anti-tumor potential of GO-Y022 on gastric cancer cell lines, KATO Ⅲ, H-111-TC, GCIY and SH-10-TC. We also examined the potential to inhibit β-Catenin and pSTAT3 levels. We conducted mouse experiment using transgenic mouse model overexpressing Wnt signaling, COX2 and Prostaglandin E2. This mouse is highly seceptible to gastric carcinogenesis. We orally administrated GO-Y022 mixed with food. We checked the safety issues of the treated mouse, and measured the tissue concentration of GO-Y022 by HPLC method. Results: GO-Y022 can inhibit the growth of gastric cancer cell lines significantly. The average IC50value of GO-Y022 was 5.05 ± 0.93 μm. That is about five times lower than curcumin. This potential was confirmed in mice. Blood concentration and the tissue distribution of GO-Y022 were negligible except gastrointestinal epithelia. GO-Y022 was safe for mouse models. Conclusions: GO-Y022 can inhibit the growth of gastric carcer in vivo. Oral administration of GO-Y022 can suppress gastic cancer topically.