Induction of apoptotic cell death by synthetic naringenin derivatives in human lung epithelial carcinoma A549 cells.
Although flavonoids, which are both qualitatively and quantitatively one of the largest groups of natural products, exhibit a variety of beneficial health effects, the exact molecular mechanism of the cellular activities is still not fully explained and there currently exists a lack of evidence for any relationship between the structure-activity relationship and apoptosis-inducing activity. In order to determine the importance of the OH group or substitution of the 5 or carbon-7 in the diphenylpropane skeleton of flavonoids, we originally synthesized several modified naringenin derivatives, including 7-O-benzyl naringenin (KUF-1) and 7-O-(MeO-L-Leu-D-Pro-carbonylmethyl) naringenin (KUF-7). Treatment with KUF-1 or KUF-7 resulted in significant apoptosis-inducing effects concomitant with chromatin condensation, caspase activation, and intracellular ROS production. Our data indicate that originally synthesized naringenin derivatives, KUF-1 and KUF-7 differentially regulate the apoptosis of A549 cells via intracellular ROS production coupled with the concomitant activation of the caspase cascade signaling pathway, thereby implying that hydroxylation or substitution at Carbon-7 is critical for the apoptosis-inducing activity of flavonoids.
Department of Animal Biotechnology, RCTCP, Konkuk University, Seoul 143- 701, Korea.
Eung-Ryoung
ER
Lee
Yong-Jin
YJ
Kang
Hye-Yeon
HY
Choi
Geun-Ho
GH
Kang
Jung-Hyun
JH
Kim
Bong-Woo
BW
Kim
Ye Sun
YS
Han
Seung-Yeol
SY
Nah
Hyun-Dong
HD
Paik
Yong-Sun
YS
Park
Ssang-Goo
SG
Cho
D000972:Antineoplastic Agents, Phytogenic; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D044950:Flavanones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005456:Fluorescent Dyes; D006801:Humans; D006900:Hydroxylation; D007211:Indoles; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D044950:Flavanones; D005456:Fluorescent Dyes; D007211:Indoles; D017382:Reactive Oxygen Species; C007293:DAPI; D053148:Caspase 3; C005273:naringenin