title: c-Jun N-terminal Kinase-Dependent Endoplasmic Reticulum Stress Pathway is Critically Involved in Arjunic Acid Induced Apoptosis in Non-Small Cell Lung Cancer Cells.
abstract: Though arjunic acid, a triterpene isolated from Terminalia arjuna, was known to have antioxidant, antiinflammatory, and cytotoxic effects, its underlying antitumor mechanism still remains unclear so far. Thus, in the present study, the molecular antitumor mechanism of arjunic acid was examined in A549 and H460 non-small cell lung cancer (NSCLC) cells. Arjunic acid exerted cytotoxicity by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT) assay and significantly increased sub-G1 population in A549 and H460 cells by cell cycle analysis. Consistently, arjunic acid cleaved poly (ADP-ribose) polymerase (PARP), activated Bax, and phosphorylation of c-Jun N-terminal kinases (JNK), and also attenuated the expression of pro-caspase-3 and Bcl-2 in A549 and H460 cells. Furthermore, arjunic acid upregulated the expression of endoplasmic reticulum (ER) stress proteins such as IRE1 α, ATF4, p-eIF2α, and C/EBP homologous protein (CHOP) in A549 and H460 cells. Conversely, CHOP depletion attenuated the increase of sub-G1 population by arjunic acid, and also JNK inhibitor SP600125 blocked the cytotoxicity and upregulation of IRE1 α and CHOP induced by arjunic acid in A549 and H460 cells. Overall, our findings suggest that arjunic acid induces apoptosis in NSCLC cells via JNK mediated ER stress pathway as a potent chemotherapeutic agent for NSCLC.
authors.affiliation: Department of East West Medical Science, Graduate School of East West Medical Science, Kyung Hee University, Suwon, South Korea.
authors.forename: HyeEun
authors.initials: H
authors.lastname: Joo
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, 130-701, South Korea.
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, 130-701, South Korea.
authors.forename: Eun Ah
authors.initials: EA
authors.lastname: Shin
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, 130-701, South Korea.
authors.forename: Hangil
authors.initials: H
authors.lastname: Kim
authors.affiliation: Graduate School of Biotechnology and Department of Oriental Medicine Biotechnology, Kyung Hee University, Yongin, 446-701, South Korea.
authors.forename: Kyeong-Hwa
authors.initials: KH
authors.lastname: Seo
authors.affiliation: Graduate School of Biotechnology and Department of Oriental Medicine Biotechnology, Kyung Hee University, Yongin, 446-701, South Korea.
authors.forename: Nam-In
authors.initials: NI
authors.lastname: Baek
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, 130-701, South Korea.
authors.forename: Bonglee
authors.initials: B
authors.lastname: Kim
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, 130-701, South Korea.
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D010766:Phosphorylation; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; C000595707:BCL2 protein, human; C497249:DDIT3 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D014315:Triterpenes; C441431:arjunic acid; D051028:bcl-2-Associated X Protein; D051742:Transcription Factor CHOP; D011065:Poly(ADP-ribose) Polymerases; D048031:JNK Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: Bax; ER stress; JNK; NSCLC; apoptosis; arjunic acid