Fisetin induces apoptosis in human nonsmall lung cancer cells via a mitochondria-mediated pathway.
The present study investigated the apoptotic effects of fisetin, a phenolic compound, against the human nonsmall cell lung cancer cell line, NCI-H460. Fisetin showed dose-dependent cytotoxic activity against NCI-H460 cells, with 50% inhibition of cell viability occurring at a concentration of 75 μg/mL. Fisetin induced both the production of intracellular reactive oxygen species and apoptosis, as evidenced by apoptotic body formation, DNA fragmentation, an increase in the number of sub-G1 phase cells, and mitochondrial membrane depolarization. Moreover, fisetin significantly modulated the expression of apoptosis-associated proteins, resulting in reduced expression of B cell lymphoma-2, increased expression of Bcl-2-associated X protein, and activation of caspase-9 and caspase-3. In addition, pretreatment with a caspase inhibitor blocked fisetin-induced cell death.
School of Medicine, Jeju National University, Jeju, 690-756, Korea.
Kyoung Ah
KA
Kang
Mei Jing
MJ
Piao
Jin Won
JW
Hyun
D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D044948:Flavonols; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008175:Lung Neoplasms / Q000201:enzymology / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D005419:Flavonoids; D044948:Flavonols; D017382:Reactive Oxygen Species; D020169:Caspases; C017875:fisetin