title: Myriocin induces apoptotic lung cancer cell death via activation of DR4 pathway.
abstract: It has been known that myriocin inhibits melanoma growth. However, the effects and action mechanisms of myriocin on lung cancer cell growth have not been reported. In this study, we examined whether myriocin isolated from Mycelia sterilia inhibits cell growth of lung cancer cells (A549 and NCI-H460) as well as possible signaling pathways involved in cell growth inhibition. Different concentrations of myriocin inhibited the growth of lung cancer cells through the induction of apoptotic cell death. Consistent with cancer cell growth inhibition, myriocin induced the expression of death receptors (DRs) as well as p-JNK and p-p38 in both cell lines. Moreover, the combination of myriocin with DR4 ligand TRAIL, and other well known anti-tumor drugs (docetaxel and cisplatin) synergistically inhibited cancer cell growth, and induced DR4 expression. These results showed that myriocin inhibits lung cancer cells growth through apoptosis via the activation of DR4 pathways, and enhanced anti-cancer effects with well known drugs. Thus, our study indicates that myriocin could be effective for lung cancer cells as an anti-cancer drug and/or a conjunction agent with well known anti-cancers.
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, 48, Gaeshin-dong, Heungduk-gu, Cheongju, 361-763, Chungbuk, Korea.
authors.forename: Kyung Eun
authors.initials: KE
authors.lastname: Choi
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Jung
authors.forename: Dea Hwan
authors.initials: DH
authors.lastname: Kim
authors.forename: Ju Kyung
authors.initials: JK
authors.lastname: Song
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Yu Yeon
authors.initials: YY
authors.lastname: Jung
authors.forename: So Young
authors.initials: SY
authors.lastname: Eum
authors.forename: Joo Hwan
authors.initials: JH
authors.lastname: Kim
authors.forename: Na Young
authors.initials: NY
authors.lastname: Yoon
authors.forename: Hwan Soo
authors.initials: HS
authors.lastname: Yoo
authors.forename: Sang-Bae
authors.initials: SB
authors.lastname: Han
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D053218:Receptors, Death Domain / Q000096:biosynthesis / Q000378:metabolism*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology; D043823:Taxoids / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D005229:Fatty Acids, Monounsaturated; D053218:Receptors, Death Domain; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; D043823:Taxoids; D000077143:Docetaxel; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D002945:Cisplatin; C001996:thermozymocidin