title: The role of autophagy induced by pemetrexed in lung adenocarcinoma cells.
abstract: Autophagy is known as an important regulatory mediator for cell survival or death and its important role in cancer. Pemetrexed (PTX) has been used in chemotherapy for lung cancer. However, the underlying molecular mechanisms have not been fully clarified. To investigate the role of autophagy induced by PTX in A549 cells, we performed MTT assay, acridine orange staining, western blotting, Annexin V/PI by using the 3-MA autophagy inhibitor. PTX induced autophagy after 48 h treatment in A549 cells. Furthermore, PTX showed acidic vesicular organelles (AVOs) and expressed LC3-II in A549 cells. The induction of autophagy by PTX was inhibited by 3-MA which was confirmed by reduced AVOs. When the autophagy was inhibited, Annexin V was increased. In addition, PARP cleavage was increased as shown by western blotting. Taken together, PTX induced autophagy in A549 cells and these cellular events possibly cause the apoptotic and/or necrotic cell death of A549 cells.
authors.affiliation: Department of Internal Medicine, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea.
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Oral Biochemistry and Institute of Biomaterials Implant, School of Dentistry, Wonkwang University, Iksan 570-749, Republic of Korea.
authors.forename: Young-Rae
authors.initials: YR
authors.lastname: Lee
authors.affiliation: Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea.
authors.forename: Hong-Seob
authors.initials: HS
authors.lastname: So
authors.affiliation: Department of Radiation Oncology, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea.
authors.forename: Kang-Kyoo
authors.initials: KK
authors.lastname: Lee
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea.
authors.forename: Sam-Youn
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Radiation Oncology, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea.
authors.forename: Sun-Rock
authors.initials: SR
authors.lastname: Moon
authors.affiliation: Department of Pathology, Gunsan Wonkwang University Hospital, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea.
authors.forename: Hyang-Jeong
authors.initials: HJ
authors.lastname: Jo
authors.affiliation: Department of Pharmacology, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea.
authors.forename: Seoul
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea.
authors.forename: Kyuyong
authors.initials: K
authors.lastname: Jeong
authors.affiliation: Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea.
authors.forename: Kang-Beom
authors.initials: KB
authors.lastname: Kwon
authors.affiliation: Department of Internal Medicine, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea.
authors.forename: Sei-Hoon
authors.initials: SH
authors.lastname: Yang
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D017304:Annexin A5 / Q000096:biosynthesis; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival; D005971:Glutamates / Q000494:pharmacology*; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D000068437:Pemetrexed; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors
chemical_list: D017304:Annexin A5; D000964:Antimetabolites, Antineoplastic; D005971:Glutamates; D000068437:Pemetrexed; C025946:3-methyladenine; D006147:Guanine; D013940:Thymidylate Synthase; D011065:Poly(ADP-ribose) Polymerases; D000225:Adenine