Didymin, a dietary flavonoid glycoside from citrus fruits, induces Fas-mediated apoptotic pathway in human non-small-cell lung cancer cells in vitro and in vivo.
Epidemiological studies provided evidence that the high dietary intake of flavonoids with fruits and vegetables could be associated with lower cancer prevalence in humans. Didymin, a dietary flavonoid glycoside from citrus fruits, possesses antioxidant properties. This study first investigates the anticancer effect of didymin in human non-small-cell lung cancer A549 and H460 cells. To identity the anticancer mechanism of didymin, we assayed its effect on apoptosis, cell cycle distribution, and levels of p53, p21/WAF1, Fas/APO-1 receptor, and Fas ligand. The results showed that didymin-induced apoptosis of A549 and H460 cells without mediation of p53 and p21/WAF1. We suggest that Fas/Fas ligand apoptotic system is the main pathway of didymin-mediated apoptosis of A549 and H460 cells. Importantly, a novel chemotherapeutic agent for the treatment of non-small-cell lung cancer, and is supported by animal studies which have shown didymin delay the tumor growth in nude mice. Our study reports here for the first time that the activity of the Fas/Fas ligand apoptotic system may participate in the antiproliferative activity of didymin in A549 and H460 cells.
Hung
Jen-Yu
JY
Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Hsu
Ya-Ling
YL
Ko
Ying-Chin
YC
Tsai
Ying-Ming
YM
Yang
Chih-Jen
CJ
Huang
Ming-Shyan
MS
Kuo
Po-Lin
PL
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002957:Citrus; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D053222:Fas Ligand Protein / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D005638:Fruit; D006027:Glycosides / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D053222:Fas Ligand Protein; D005419:Flavonoids; D006027:Glycosides; D016159:Tumor Suppressor Protein p53; C552234:didymin; D019014:fas Receptor