title: ω-Hydroxyundec-9-enoic acid induces apoptosis through ROS-mediated endoplasmic reticulum stress in non-small cell lung cancer cells.
abstract: ω-Hydroxyundec-9-enoic acid (ω-HUA), a hydroxyl unsaturated fatty acid derivative, is involved in the antifungal activity of wild rice (Oryza officinalis). Here, we investigated the anti-cancer activity of ω-HUA on a non-small cell lung cancer (NSCLC) cell line. ω-HUA increased apoptosis and induced cleavages of caspase-6, caspase-9, and poly (ADP-ribose) polymerase (PARP). ω-HUA treatment significantly induced endoplasmic reticulum (ER) stress response. Suppression of CHOP expression and inhibiting ER stress by 4-phenylbutyrate (4-PBA) significantly attenuated the ω-HUA treatment-induced activation of caspase-6, caspase-9, and PARP, and subsequent apoptotic cell death, indicating a role for ER stress in ω-HUA-induced apoptosis. In addition, cells subjected to ω-HUA exhibited significantly increased quantity of reactive oxygen species (ROS), and the ROS scavenger N-acetyl-L-cysteine (NAC) inhibited ω-HUA-induced apoptotic cell death and ER stress signals, indicating a role for ROS in ER stress-mediated apoptosis in ω-HUA-treated cells. Taken together, these results suggest that sequential ROS generation and ER stress activation are critical in ω-HUA treatment-induced apoptosis and that ω-HUA represents a promising candidate for NSCLC treatment.
authors.affiliation: Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul 120-749, Republic of Korea.
authors.forename: Kyung Mi
authors.initials: KM
authors.lastname: Yang
authors.affiliation: Division of Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Byeong Mo
authors.initials: BM
authors.lastname: Kim
authors.affiliation: Department of Food Science and Engineering, Ewha Womans University, Seoul 120-750, Republic of Korea. Electronic address: jbpark06@ewha.ac.kr.
authors.forename: Jin-Byung
authors.initials: JB
authors.lastname: Park
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053178:Caspase 6 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014476:Undecylenic Acids / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; C497249:DDIT3 protein, human; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D014476:Undecylenic Acids; C000590836:omega-hydroxyundec-9-enoic acid; D051742:Transcription Factor CHOP; D011065:Poly(ADP-ribose) Polymerases; C505514:CASP6 protein, human; C506433:CASP9 protein, human; D053178:Caspase 6; D053453:Caspase 9; D000111:Acetylcysteine
keywords: Apoptosis; Endoplasmic reticulum (ER) stress; N-Acetyl-l-cysteine (NAC); Non-small cell lung cancer (NSCLC); Reactive oxygen species (ROS); ω-Hydroxyundec-9-enoic acid (ω-HUA)