title: The anticancer potential of steroidal saponin, dioscin, isolated from wild yam (Dioscorea villosa) root extract in invasive human breast cancer cell line MDA-MB-231 in vitro.
abstract: Previously, we observed that wild yam (Dioscorea villosa) root extract (WYRE) was able to activate GATA3 in human breast cancer cells targeting epigenome. This study aimed to find out if dioscin (DS), a bioactive compound of WYRE, can modulate GATA3 functions and cellular invasion in human breast cancer cells. MCF-7 and MDA-MB-231 cells were treated in the absence/presence of various concentrations of DS and subjected to gene analysis by RT-qPCR, immunoblotting, and immunocytochemistry. We determined the ability of MDA-MB-231 cells to migrate into wound area and examined the effects of DS on cellular invasion using invasion assay. DS reduced cell viability of both cell lines in a concentration and time-dependent manner. GATA3 expression was enhanced by DS (5.76 μM) in MDA-MB-231 cells. DS (5.76 μM)-treated MDA-MB-231 cells exhibited the morphological characteristic of epithelial-like cells; mRNA expression of DNMT3A, TET2, TET3, ZFPM2 and E-cad were increased while TET1, VIM and MMP9 were decreased. Cellular invasion of MDA-MB-231 was reduced by 65 ± 5% in the presence of 5.76 μM DS. Our data suggested that DS-mediated pathway could promote GATA3 expression at transcription and translation levels. We propose that DS has potential to be used as an anti-invasive agent in breast cancer.
authors.affiliation: National Center for Natural Product Research, School of Pharmacy, University of Mississippi, University, MS 38677, USA; Division of Pharmacology, Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS 38677, USA.
authors.forename: Pranapda
authors.initials: P
authors.lastname: Aumsuwan
authors.affiliation: National Center for Natural Product Research, School of Pharmacy, University of Mississippi, University, MS 38677, USA; Division of Pharmacognosy, Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS 38677, USA.
authors.forename: Shabana I
authors.initials: SI
authors.lastname: Khan
authors.affiliation: National Center for Natural Product Research, School of Pharmacy, University of Mississippi, University, MS 38677, USA; Division of Pharmacognosy, Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS 38677, USA.
authors.forename: Ikhlas A
authors.initials: IA
authors.lastname: Khan
authors.affiliation: National Center for Natural Product Research, School of Pharmacy, University of Mississippi, University, MS 38677, USA.
authors.forename: Zulfiqar
authors.initials: Z
authors.lastname: Ali
authors.affiliation: National Center for Natural Product Research, School of Pharmacy, University of Mississippi, University, MS 38677, USA.
authors.forename: Bharathi
authors.initials: B
authors.lastname: Avula
authors.affiliation: National Center for Natural Product Research, School of Pharmacy, University of Mississippi, University, MS 38677, USA; Division of Pharmacology, Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS 38677, USA; University of Mississippi Cancer Institute (Oxford Campus), School of Pharmacy, University of Mississippi, University, MS 38677, USA.
authors.forename: Larry A
authors.initials: LA
authors.lastname: Walker
authors.affiliation: Division of Pharmacology, Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS 38677, USA.
authors.forename: Zia
authors.initials: Z
authors.lastname: Shariat-Madar
authors.affiliation: Department of Food Science and Human Nutrition, University of Illinois, Urbana, IL 61801, USA.
authors.forename: William G
authors.initials: WG
authors.lastname: Helferich
authors.affiliation: Department of Molecular and Integrative Physiology, University of Illinois, Urbana, IL 61801, USA.
authors.forename: Benita S
authors.initials: BS
authors.lastname: Katzenellenbogen
authors.affiliation: National Center for Natural Product Research, School of Pharmacy, University of Mississippi, University, MS 38677, USA; Division of Pharmacology, Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS 38677, USA; University of Mississippi Cancer Institute (Oxford Campus), School of Pharmacy, University of Mississippi, University, MS 38677, USA. Electronic address: asok@olemiss.edu.
authors.forename: Asok K
authors.initials: AK
authors.lastname: Dasmahapatra
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D027742:Dioscorea / Q000737:chemistry*; D004144:Diosgenin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D061986:MCF-7 Cells; D009361:Neoplasm Invasiveness; D010840:Phytosterols / Q000008:administration & dosage; D010936:Plant Extracts / Q000008:administration & dosage*; D018517:Plant Roots / Q000737:chemistry*; D012503:Saponins / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010840:Phytosterols; D010936:Plant Extracts; D012503:Saponins; C019357:dioscin; D004144:Diosgenin
keywords: Dioscin; GATA3; Gene expression; Invasion/migration; ZFPM2