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.
Lee
Eung-Ryoung
ER
Department of Animal Biotechnology, RCTCP, Konkuk University, Seoul 143- 701, Korea.
Kang
Yong-Jin
YJ
Choi
Hye-Yeon
HY
Kang
Geun-Ho
GH
Kim
Jung-Hyun
JH
Kim
Bong-Woo
BW
Han
Ye Sun
YS
Nah
Seung-Yeol
SY
Paik
Hyun-Dong
HD
Park
Yong-Sun
YS
Cho
Ssang-Goo
SG
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