title: AECHL-1 targets breast cancer progression via inhibition of metastasis, prevention of EMT and suppression of Cancer Stem Cell characteristics.
abstract: Triple negative breast cancer (TNBC) features among the most aggressive manifestations of cancer due to its enhanced metastatic potential and immunity to therapeutics which target hormone receptors. Under such scenarios, anti-cancer compounds with an ability to influence multiple targets, or an entire process, will have an advantage over specific signal transduction inhibitors. To counter the metastatic threat it is essential to target cellular components central to the processes of cancer cell migration and adaptation. Our previous work on a novel triterpenoid, AECHL-1, explored its anti-cancer potential, and linked it to elevated ER stress in cancer cells, while its anti-angiogenic potential was credited for its ability to manipulate the cytoskeleton. Here, we broaden its range of action by showing that it curbs the metastatic ability of TNBC cells, both in vitro in MDA-MB-231 cell line and in vivo, in mouse models of metastasis. AECHL-1 does so by disrupting the cytoskeletal network, and also suppressing NF-κB and β-Catenin mediated key molecular pathways. These activities also contributed to AECHL-1 mediated suppression of TGF-β/TNF-α induced Epithelial to Mesenchymal Transition (EMT) and cancer stem cell characteristic. Thus, we present AECHL-1 as a promising therapeutic inhibitor of metastatic disease.
authors.affiliation: National Centre for Cell Science, NCCS Complex, S.P. Pune University, Ganeshkhind, Pune 411007, Maharashtra, India.
authors.forename: Aparajita
authors.initials: A
authors.lastname: Dasgupta
authors.affiliation: National Centre for Cell Science, NCCS Complex, S.P. Pune University, Ganeshkhind, Pune 411007, Maharashtra, India.
authors.forename: Mithila A
authors.initials: MA
authors.lastname: Sawant
authors.affiliation: National Centre for Cell Science, NCCS Complex, S.P. Pune University, Ganeshkhind, Pune 411007, Maharashtra, India.
authors.forename: Gayatri
authors.initials: G
authors.lastname: Kavishwar
authors.affiliation: Pharmazz India Private Limited, H-6, Site-C, Surajpur Industrial area, Greater Noida, UP- 201307, India.
authors.forename: Manish
authors.initials: M
authors.lastname: Lavhale
authors.affiliation: National Centre for Cell Science, NCCS Complex, S.P. Pune University, Ganeshkhind, Pune 411007, Maharashtra, India.
authors.forename: Sandhya
authors.initials: S
authors.lastname: Sitasawad
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D014315:Triterpenes / Q000008:administration & dosage* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000378:metabolism
chemical_list: C000606400:AECHL-1 compound; C495270:CTNNB1 protein, human; D016328:NF-kappa B; D014315:Triterpenes; D051176:beta Catenin