title: Baicalein Induces Caspase-dependent Apoptosis Associated with the Generation of ROS and the Activation of AMPK in Human Lung Carcinoma A549 Cells.
abstract: Baicalein is one of the main bioactive flavonoids found in the roots of Scutellaria baicalensis Georgi. Here, we report that baicalein-induced growth inhibition was associated with the induction of apoptosis in human lung carcinoma A549 cells. Baicalein stimulated the expression of DR5, FasL, and FADD, and activated caspase-8 by reducing the levels of FLIPs (FLICE-inhibitory proteins). The apoptotic cell death was also connected with an activation of caspase-9 and -3, and cleavage of poly(ADP-ribose) polymerase; however, a blockage of caspase activation abolished baicalein-induced apoptotic potentials. Additionally, baicalein caused a mitochondrial membrane potential (MMP), the truncation of Bid, and the translocation of pro-apoptotic Bax to the mitochondria, thereby inducing the release of cytochrome c into the cytosol. In turn, baicalein increased the generation of reactive oxygen species (ROS); however, an ROS scavenger, N-acetylcysteine, notably attenuated baicalein-mediated loss of MMP and activation of caspases. Furthermore, baicalein activated the AMP-activated protein kinase (AMPK) signaling pathway. Consequently, baicalein-triggered cell death was attenuated by an AMPK inhibitor, but increased by an AMPK activator, compound C. Overall, the results suggest that the apoptotic activity of baicalein may be associated with caspase-dependent cascade through the activation of both intrinsic and extrinsic signaling pathways connected with ROS generation and AMPK activation.
authors.affiliation: Department of Pharmacy, College of Pharmacy, Pusan National University, Busan, 609-735, South Korea.|Anti-Aging Research Center, Dongeui University, Busan, 614-714, South Korea.
authors.forename: Hong Jae
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Molecular Biology, College of Natural Sciences and Human Ecology, Dongeui University, Busan, 614-714, South Korea.
authors.forename: Cheol
authors.initials: C
authors.lastname: Park
authors.affiliation: Natural Products Research Team, National Marine Biodiversity Institute of Korea, Seocheon, 325-902, South Korea.
authors.forename: Min-Ho
authors.initials: MH
authors.lastname: Han
authors.affiliation: Department of Biochemistry, Dongeui University College of Korean Medicine, Busan, 614-052, South Korea.
authors.forename: Su-Hyun
authors.initials: SH
authors.lastname: Hong
authors.affiliation: Department of Marine Life Sciences, Jeju National University, Jeju, 690-756, South Korea.
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Dongeui University College of Korean Medicine, Busan, 614-052, South Korea.
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Hong
authors.affiliation: Department of Pharmacy, College of Pharmacy, Pusan National University, Busan, 609-735, South Korea.
authors.forename: Nam Deuk
authors.initials: ND
authors.lastname: Kim
authors.affiliation: Anti-Aging Research Center, Dongeui University, Busan, 614-714, South Korea.|Department of Biochemistry, Dongeui University College of Korean Medicine, Busan, 614-052, South Korea.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D044950:Flavanones / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D044950:Flavanones; D017382:Reactive Oxygen Species; C006680:baicalein; D055372:AMP-Activated Protein Kinases; D020169:Caspases
keywords: A549 cells; AMPK; ROS; apoptosis; baicalein; caspase