title: ROS-mediated activation of JNK/p38 contributes partially to the pro-apoptotic effect of ajoene on cells of lung adenocarcinoma.
abstract: Ajoene, a garlic-derived organosulfur compound, exerts anti-tumorigenic effect against various cancers. However, little is known about the biological effect of ajoene on lung adenocarcinoma, an aggressive malignancy with dismal prognosis. We investigated the biological effect of ajoene on lung adenocarcinoma and the underlying pathway. Lung adenocarcinoma cells A549, NCI-H1373, and NCI-H1395, along with the noncancerous lung bronchus cells BEAS-2B, were used. MTT test showed that ajoene (25 μM) reduces viability of lung adenocarcinoma cells but not the noncancerous BEAS-2B cells. Bromodeoxyuridine incorporation assay revealed that ajoene inhibits proliferation of lung adenocarcinoma cells. Treatment of lung adenocarcinoma cells with ajoene enhances apoptosis and ROS generation in a time- and dose-dependent fashion. Abrogation of caspase activation by zVAD-fmk completely prevents the ajoene-induced apoptosis; whereas block of ROS generation by N-acetylcysteine partly abolishes the ajoene-induced apoptosis. ROS-mediated induction of apoptosis contributes partially to the anti-tumorigenic property of ajoene observed, a phenomenon also confirmed by xenograft tumor study. Mitogen activated protein kinases (MAPKs), pivots of ROS-mediated signaling pathway, are activated upon ajoene treatment; Jun-N-terminal kinase (JNK)/p38 activations are required for signaling pathway underlying the ajoene-induced apoptosis. Our results suggest that ROS-mediated activation of JNK/p38 contributes partially to the pro-apoptotic action of ajoene on cells of lung adenocarcinoma. Ajoene may be a promising chemotherapeutic agent for lung adenocarcinoma.
authors.affiliation: Oncology Department of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, NO. 1, ShuaiFuYuan Hutong, Dongcheng District, Beijing, 100730, People's Republic of China.
authors.forename: Yingyi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Oncology Department of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, NO. 1, ShuaiFuYuan Hutong, Dongcheng District, Beijing, 100730, People's Republic of China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Oncology Department of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, NO. 1, ShuaiFuYuan Hutong, Dongcheng District, Beijing, 100730, People's Republic of China.
authors.forename: Shuchang
authors.initials: S
authors.lastname: Chen
authors.affiliation: Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular Oncology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Beijing, 100021, People's Republic of China.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Oncology Department of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, NO. 1, ShuaiFuYuan Hutong, Dongcheng District, Beijing, 100730, People's Republic of China. baichunmei2001@163.com.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Bai
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D061945:Caspase Inhibitors / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004220:Disulfides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008819:Mice, Nude; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013454:Sulfoxides; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D004220:Disulfides; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D013454:Sulfoxides; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C048980:ajoene; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases
keywords: Adenocarcinoma; Ajoene; Apoptosis; Lung; MAPKs; ROS