title: Role of autophagy in apoptosis induction by methylene chloride extracts             of Mori cortex in NCI-H460 human lung carcinoma cells.
abstract: The root of Mori cortex has traditionally been used in Korea for the treatment             of cutaneous inflammation, pulmonary asthma, and congestion for thousands of years.             The present study was designed to validate the anticancer effects of methylene             chloride extracts of the M. cortex root (MEMC) in NCI-H460 human lung carcinoma             cells. Exposure to MEMC was found to result in growth inhibition by the induction             of caspase‑dependent apoptosis in NCI-H460 cells, which correlated with upregulated             expression of death receptor (DR)4, DR5 and FasL, downregulation of anti-apoptotic             Bcl-2 and Bcl-xL expression, cleavage of Bid, and loss of mitochondrial membrane             potential. In addition, autophagosomes, a characteristic finding of autophagy,             and markers of autophagy, conversion of microtubule-associated protein light chain-3             (LC3)-I to LC3-II and increased beclin-1 accumulation, were observed in MEMC-treated             NCI-H460 cells. Inhibition of autophagy by 3-methyladenine or LC3B small interfering             (siRNA) resulted in enhanced apoptotic cell death, suggesting that MEMC-induced             autophagy functions as a suppressor of apoptosis. MEMC-induced autophagy was also             blocked by N-acetyl-cysteine (NAC) and catalase, indicating that H2O2 can regulate             autophagy. Our data demonstrate that MEMC triggers both ROS-mediated autophagy             and caspase-dependent apoptosis, and that autophagy plays a protective role against             apoptotic cell death.
authors.affiliation: Department of Pathology, College of Oriental Medicine and Research Institute of Oriental Medicine, Dongeui University, Busan 614-052, Republic of Korea.
authors.forename: Shin-Hyung
authors.initials: SH
authors.lastname: Park
authors.forename: Gyoo Yong
authors.initials: GY
authors.lastname: Chi
authors.forename: Hyun Sup
authors.initials: HS
authors.lastname: Eom
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Hyun
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
authors.forename: Su-Jae
authors.initials: SJ
authors.lastname: Lee
authors.forename: Young Hyun
authors.initials: YH
authors.lastname: Yoo
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D008518:Medicine, East Asian Traditional; D053078:Membrane Potential, Mitochondrial; D008752:Methylene Chloride / Q000737:chemistry*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D012997:Solvents / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C502070:MAP1LC3B protein, human; D008869:Microtubule-Associated Proteins; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D012997:Solvents; D008752:Methylene Chloride; D020169:Caspases