title: Calycosin induces apoptosis in colorectal cancer cells, through modulating the ERβ/MiR-95 and IGF-1R, PI3K/Akt signaling pathways.
abstract: Calycosin, the main component extractable from the herb Radix astragali, has been shown to inhibit cellular proliferation and induce apoptosis in several cancer cell lines, but the underlying mechanisms by the way in which this occurs remain unclear. In the present study, we aimed to determine the potential effects of calycosin on proliferation in colorectal cancer cells in vitro and in vivo and to elucidate the underlying molecular mechanisms of action. Colorectal cancer cell lines SW480 and LoVo and cervical cancer cell line HeLa were treated with various concentrations of calycosin or plus ER beta (ERβ) inhibitor PHTPP. The CCK8 assay, flow cytometry, and Hoechst 33258 stain were used to assess the effects on cellular proliferation and apoptosis. The mRNA levels of ERβ and miR-95 were quantified by real-time PCR. The protein expression levels of ERβ, ERα, IGF-1R, and p-Akt were evaluated by Western blot analysis. We demonstrated that calycosin inhibited the proliferation in SW480 and LoVo cells and induced apoptosis, particularly in SW480 cells, but not in HeLa cells. Calycosin increased ERβ expression and reduced the ERα, IGF-1R, and p-Akt expression alongside down-regulation of miR-95 in SW480 cells. Inhibiting ERβ blocked the change of miR-95 and the resulting increase in apoptosis in SW480 cells. Additionally, calycosin significantly suppressed xenograft tumor growth in nude mice. In conclusion, calycosin exerts an inhibitory effect on proliferation of CRC cells in vivo and in vitro, through ERβ-mediated regulation of the IGF-1R, PI3K/Akt signaling pathways and of miR-95 expression.
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Guilin Medical University, Guilin 541004, China.
authors.forename: Xinge
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Guilin Medical University, Guilin 541004, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Guilin Medical University, Guilin 541004, China.
authors.forename: Qianyao
authors.initials: Q
authors.lastname: Ren
authors.affiliation: Department of Physiology, School of Basic Medical Sciences, Guilin Medical University, Guilin 541004, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Guilin Medical University, Guilin 541004, China. Electronic address: Chenjian5268@163.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D047629:Estrogen Receptor beta; D007529:Isoflavones; C575854:MIRN95 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C121707:7,3'-dihydroxy-4'-methoxyisoflavone; D019869:Phosphatidylinositol 3-Kinases; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; Calycosin; Colorectal cancer; ERβ; miR-95