title: Azorella compacta methanolic extract induces apoptosis via activation of mitogen-activated protein kinase.
abstract: Azorella compacta Phil. (AC) is an alpine medicinal plant used traditionally for antibacterial treatment. Recent studies have revealed that this plant also has anti‑diabetic effects, but that it is toxic. The present study investigated the underlying mechanisms of action of AC extract against human leukemia HL60 cells. Apoptosis induction was measured by MTT assay, fluorescence microscopy, DNA fragmentation assay, flow cytometric analysis, reverse transcription quantitative polymerase chain reaction and western blot analyses. It was found that AC extract inhibited the growth of HL60 and other cancer cell lines in a dose‑dependent manner. The cytotoxic effects of AC extract on HL60 cells were associated with apoptosis characterized by DNA fragmentation and dose‑dependent increases in Annexin V‑positive cells, as determined by flow cytometric analysis. AC‑extract‑induced apoptosis was accompanied by activated/cleaved caspase‑3, caspase‑9 and poly(adenosine diphosphate‑ribose) polymerase (PARP). The increases in apoptosis were also associated with decreases of the apoptosis-inhibitor B-cell lymphoma 2 (Bcl‑2), upregulation of pro‑apoptotic Bcl-2-associated X (Bax) protein and downregulation of anti‑apoptotic Bcl extra large protein. Furthermore, western blot analysis of mitogen-activated protein kinase (MAPK)-associated proteins indicated that treatment with AC extract increased the levels of c-Jun N-terminal kinase, extracellular signal-regulated kinase and p38. In addition, the expression of Bax and cleaved PARP was blocked when AC treatment was performed in the presence of MAPK inhibitors. It was therefore concluded that AC induced apoptosis in human leukemia HL60 cells via an intrinsic pathway controlled through MAPK-associated signaling.
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Chungbuk 363‑883, Republic of Korea.
authors.forename: Min Hee
authors.initials: MH
authors.lastname: Sung
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Chungbuk 363‑883, Republic of Korea.
authors.forename: Ok-Kyoung
authors.initials: OK
authors.lastname: Kwon
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Chungbuk 363‑883, Republic of Korea.
authors.forename: Sei-Ryang
authors.initials: SR
authors.lastname: Oh
authors.affiliation: International Biological Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
authors.forename: Joongku
authors.initials: J
authors.lastname: Lee
authors.affiliation: International Biological Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
authors.forename: Sang-Hong
authors.initials: SH
authors.lastname: Park
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361‑763, Republic of Korea.
authors.forename: Sang Bae
authors.initials: SB
authors.lastname: Han
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Chungbuk 363‑883, Republic of Korea.
authors.forename: Kyung-Seop
authors.initials: KS
authors.lastname: Ahn
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D019661:Apiaceae / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation; D018922:HL-60 Cells; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D020935:MAP Kinase Signaling System; D000432:Methanol / Q000737:chemistry; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D012997:Solvents / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D010936:Plant Extracts; D012997:Solvents; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases; D000432:Methanol