title: Asperjinone, a nor-neolignan, and terrein, a suppressor of ABCG2-expressing breast cancer cells, from thermophilic Aspergillus terreus.
abstract: Breast cancer cells express ABCG2 transporters, which mediate multidrug resistance. Discovering a novel compound that can suppress ABCG2 expression and restore drug sensitivity could be the key to improving breast cancer therapeutics. In the current work, one new nor-neolignan, asperjinone (1), as well as 12 other known compounds, was isolated from Aspergillus terreus. The structure of the new isolate was determined by spectroscopic methods. Among these isolates, terrein (2) displayed strong cytotoxicity against breast cancer MCF-7 cells. Treatment with terrein (2) significantly suppressed growth of ABCG2-expressing breast cancer cells. This suppressive effect was achieved by inducing apoptosis via activating the caspase-7 pathway and inhibiting the Akt signaling pathway, which led to a decrease in ABCG2-expressing cells and a reduction in the side-population phenotype.
authors.affiliation: Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung 402, Taiwan, Republic of China.
authors.forename: Wen-Ying
authors.initials: WY
authors.lastname: Liao
authors.forename: Chia-Ning
authors.initials: CN
authors.lastname: Shen
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Lin
authors.forename: Yu-Liang
authors.initials: YL
authors.lastname: Yang
authors.forename: Hsin-Ying
authors.initials: HY
authors.lastname: Han
authors.forename: Jing-Wei
authors.initials: JW
authors.lastname: Chen
authors.forename: Sheng-Chu
authors.initials: SC
authors.lastname: Kuo
authors.forename: Shih-Hsiung
authors.initials: SH
authors.lastname: Wu
authors.forename: Chih-Chuang
authors.initials: CC
authors.lastname: Liaw
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000187:drug effects*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001230:Aspergillus / Q000737:chemistry*; D001943:Breast Neoplasms / Q000378:metabolism; D053179:Caspase 7 / Q000235:genetics / Q000378:metabolism; D003517:Cyclopentanes / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D015394:Molecular Structure; D009363:Neoplasm Proteins / Q000187:drug effects*; D019906:Nuclear Magnetic Resonance, Biomolecular; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects; D013624:Taiwan
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D003517:Cyclopentanes; D017705:Lignans; D009363:Neoplasm Proteins; C573520:asperjinone; C439087:terrein; D051057:Proto-Oncogene Proteins c-akt; D053179:Caspase 7