title: 25-methoxyl-dammarane-3β, 12β, 20-triol and artemisinin synergistically inhibit MDA-MB-231 cell proliferation through downregulation of testes-specific protease 50 (TSP50) expression.
abstract: While the incidence of cancer continues to increase, the current therapeutic options remain imperfect. Therefore, there is an urgent need to discover new targeted anti-cancer therapies. Testes-specific protease 50 (TSP50) is abnormally expressed in most cancer tissues and downregulation of TSP50 expression can reduce cell proliferation and induce cell apoptosis, which makes it a potential target for cancer therapy. In this study, we constructed a firefly luciferase reporter pGL3-TSP50-3'-UTR as a drug screening model to screen potential candidate compounds that target TSP50 mRNA. We identified the compound 7P3A, which consists of 70 % 25-methoxyl-dammarane-3β, 12β, 20-triol and 30 % artemisinin, as being capable of inhibiting the TSP50-3'-UTR reporter activity, as well as the expression of TSP50. Further investigation revealed that 7P3A could inhibit MDA-MB-231 cell proliferation and induce cell cycle arrest, and over-expression of TSP50 partially reversed the effect of 7P3A. In vivo investigation showed that 7P3A could inhibit tumor growth in a xenograft model of breast cancer. These results suggest that 7P3A exhibits anti-cancer effects, in part, through downregulation of TSP50 expression.
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, 130024, China.|Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education, Northeast Normal University, Changchun, 130024, China.
authors.forename: Danfeng
authors.initials: D
authors.lastname: Wang
authors.affiliation: Food Science Engineering, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, 130024, China.|Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education, Northeast Normal University, Changchun, 130024, China.
authors.forename: Yimeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education, Northeast Normal University, Changchun, 130024, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Rong
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, 130024, China.
authors.forename: Hongshuang
authors.initials: H
authors.lastname: Qin
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, 130024, China. baoyl800@nenu.edu.cn.
authors.forename: Yongli
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education, Northeast Normal University, Changchun, 130024, China.
authors.forename: Zhenbo
authors.initials: Z
authors.lastname: Song
authors.affiliation: Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education, Northeast Normal University, Changchun, 130024, China.
authors.forename: Chunlei
authors.initials: C
authors.lastname: Yu
authors.affiliation: Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education, Northeast Normal University, Changchun, 130024, China.
authors.forename: Luguo
authors.initials: L
authors.lastname: Sun
authors.affiliation: Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education, Northeast Normal University, Changchun, 130024, China. liyx486@nenu.edu.cn.|Institute of Genetics and Cytology, Northeast Normal University, Changchun, 130024, China. liyx486@nenu.edu.cn.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D037621:Artemisinins / Q000008:administration & dosage; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects* / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012502:Sapogenins / Q000008:administration & dosage; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: C557882:25-methoxyldammarane-3,12,20-triol; D020413:3' Untranslated Regions; D000962:Antimalarials; D037621:Artemisinins; D012502:Sapogenins; D012697:Serine Endopeptidases; C446379:testis-specific protease 50
keywords: 25-methoxyl-dammarane-3β, 12β, 20-triol; 7P3A; Artemisinin; Cell cycle; Proliferation; TSP50