title: Inhibition of silibinin on migration and adhesion capacity of human highly metastatic breast cancer cell line, MDA-MB-231, by evaluation of β1-integrin and downstream molecules, Cdc42, Raf-1 and D4GDI.
abstract: Metastasis is a property of malignant cancer cells that requires integrins which with their downstream molecules participate in a number of signaling events in cells with pivotal roles in malignancy, migration and invasion of tumor cells. Silibinin, a flavonoid antioxidant from milk thistle (Silybum marianum L.), has attracted attention in the last decades for chemoprevention and chemotherapy of tumor cells. In the present study, the effect of silibinin on migration and adhesion capacity of MDA-MB-231 cells, a highly metastatic human breast cancer cell line, was investigated by evaluation of β1-integrin and its important downstream molecules. MTT, migration and adhesion assays were performed to evaluate the silibinin effects on proliferation, migration and adhesion of MDA-MB-231 cells. In addition, the influence of the silibinin on the expression of β1-integrin, Raf-1, Cdc42 and D4-GDI mRNAs was assessed by RT-PCR. Results showed significant dose-dependent inhibitory effect of silibinin on proliferation, migration and adhesion of MDA-MB-231 cells. It significantly inhibited the expression of Cdc42 and D4-GDI mRNAs but had no statistically significant effect on the expression of β1-integrin and Raf-1 mRNAs although it indirectly but effectively modulated β1-integrin signaling pathway and RAF1 function. In conclusion, the results showed the silibinin effectson reducing the rate of metastasis, migration and adhesion of MDA-MB-231 to distant organs.
authors.affiliation: Department of Molecular and Cellular Biology, University of Tehran, Tehran, Iran.
authors.forename: Mohadeseh
authors.initials: M
authors.lastname: Dastpeyman
authors.forename: Nasrin
authors.initials: N
authors.lastname: Motamed
authors.forename: Kayhan
authors.initials: K
authors.lastname: Azadmanesh
authors.forename: Ehsan
authors.initials: E
authors.lastname: Mostafavi
authors.forename: Vahid
authors.initials: V
authors.lastname: Kia
authors.forename: Ali
authors.initials: A
authors.lastname: Jahanian-Najafabadi
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Shokrgozar
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics*; D009362:Neoplasm Metastasis; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D020764:cdc42 GTP-Binding Protein / Q000235:genetics*; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta / Q000235:genetics*
chemical_list: C569658:ARHGDIB protein, human; D000975:Antioxidants; D019012:Integrin beta1; D012333:RNA, Messenger; D012838:Silymarin; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D000077385:Silybin; D019908:Proto-Oncogene Proteins c-raf; D020764:cdc42 GTP-Binding Protein
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