title: Cryptotanshinone inhibits breast cancer cell growth by suppressing estrogen receptor signaling.
abstract: Estrogen receptor (ER) is a major therapeutic target for the treatment of breast cancer, because of the crucial role of estrogen signaling deregulation in the development and progression of breast cancer. In this study, we report the identification of a novel ERα binding compound, cryptotanshinone (CPT), by screening the CADD database. We also show that CPT effectively inhibits estrogen-induced ER transactivation and gene expression of ER target genes. Furthermore, we showed that CPT suppressed breast cancer cell growth mainly in an ERα dependent manner. Finally, we confirmed the potential therapeutic efficiency of CPT using xenograft experiments in vivo. Taken together, our results describe a novel mechanism for the anticancer activity of CPT and provide supporting evidence for its use as a potential therapeutic agent to treat patients with ERα positive breast cancer.
authors.affiliation: a Laboratory of Medical Molecular Biology; Beijing Institute of Biotechnology ; Beijing , PR China.
authors.forename: Shanhu
authors.initials: S
authors.lastname: Li
authors.forename: Hongtao
authors.initials: H
authors.lastname: Wang
authors.forename: Liu
authors.initials: L
authors.lastname: Hong
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Fang
authors.initials: F
authors.lastname: Huang
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Zhang
authors.forename: Jianguang
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D010616:Phenanthrenes / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D011960:Receptors, Estrogen / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014158:Transcription, Genetic; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D047628:Estrogen Receptor alpha; D010616:Phenanthrenes; D011960:Receptors, Estrogen; C037886:cryptotanshinone
keywords: CADD, computer-aided drug design; CPT, cryptotanshinone; ER, estrogen receptor; EREs, estrogen-responsive elements; ROS, reactive oxygen species; SERM, selective estrogen receptor modulator; breast cancer; cryptotanshinone; estradiol; estrogen receptor