Combination effects of nobiletin and celecoxib on the growth inhibition of colon cancer cells

• Main Authors: Ya-Chi Sun, 孫雅祺
• Other Authors: Wenchang Chiang
• Format: Others
• Language: zh-TW
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/94643794301713084675

碩士 === 國立臺灣大學 === 食品科技研究所 === 99 === Nobiletin, a polymethoxyflavones isolated from citrus peels, could inhibit the COX-2 expression in various cancer cells and lead to cell cycle arrest. A non-steroidal anti-inflammatory drug (NSAID), celecoxib has been approved by the US Food and Drug Administration for the adjunctive therapy in patients with familial adenomatous polyposis (FAP) or colon cancer. However, celecoxib treatment causes undesired side effects, including gastrointestinal and cardiovascular toxicities. Thus, it would be beneficial if combination treatment to provide enhanced therapeutic response and reduce the side effects of medication. HT-29 and COLO-205 human colon cancer cells exposed to various doses of celecoxib, nobiletin and co-treated with both agents were analyzed for cell proliferation, cell cycle analysis by propidium iodide staining, apoptosis analysis by annexin V/PI staining and γH2AX expression by immunofluorescence and western blotting analysis. Our results show that adding nobiletin to subtoxic celecoxib could synergistically or additively inhibit cell proliferation. Particularly, 75 μM celecoxib together with 50 μM nobiletin indicated the synergistic effect. Combining celecoxib with nobiletin significantly increases DNA damage signal, γH2AX levels and concurrently inhibits cell proliferations and promotes cell death by apoptosis. These results suggest that celecoxib-nobiletin co-treatment may provide enhanced therapeutic response in colon cancer cells, while avoiding the toxicity associated with high-dose celecoxib treatment.