The flavonoid quercetin induces apoptosis and inhibits migration through a MAPK-dependent mechanism in osteoblasts.
The present study was undertaken to evaluate effects of quercetin, a major dietary flavonoid occurring in foods of plant origin, on cell viability and migration of osteoblastic cells. Quercetin inhibited cell viability, which was largely attributed to apoptosis, in a dose-and time-dependent manner in osteoblastic cells. Similar cytotoxicity of quercetin was observed in adipose tissue-derived stromal cells. Quercetin exerted a protective effect against H(2)O(2)-induced cell death, whereas it increased TNF-alpha-induced cell death. Western blot analysis showed that quercetin induced activation of ERK and p38, but not JNK. Quercetin-induced cell death was prevented by the ERK inhibitor PD98059, but not by inhibitors of p38 and JNK. Quercetin increased Bax expression and caused depolarization of mitochondrial membrane potential, which were inhibited by PD98059. Quercetin induced caspase-3 activation, and the quercetininduced cell death was prevented by caspase inhibitors. Quercetin inhibited cell migration, and its effect was prevented by inhibitors of ERK and p38. Taken together, these findings suggest that quercetin induces apoptosis through a mitochondria-dependent mechanism involving ERK activation and inhibits migration through activation of ERK and p38 pathways. Quercetin may exert both protective and deleterious effects in bone repair.
Nam
Tae Wook
TW
Department of Orthopedic Surgery, Pusan National University, Pusan, Korea.
Yoo
Chong Il
CI
Kim
Hui Taek
HT
Kwon
Chae Hwa
CH
Park
Ji Yeon
JY
Kim
Yong Keun
YK
D016475:3T3 Cells; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D016877:Oxidants / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000975:Antioxidants; D004791:Enzyme Inhibitors; D044950:Flavanones; D005419:Flavonoids; D016877:Oxidants; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; C006680:baicalein; D011794:Quercetin; D006861:Hydrogen Peroxide; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one