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Antiproliferative activity exerted by tricyclohexylphosphanegold(I) n-mercaptobenzoate against MCF-7 and A2780 cell lines: the role of p53 signaling pathways.
Ang, Kok Pian; Chan, Pit Foong; Hamid, Roslida Abd.
Afiliação
  • Ang KP; Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.
  • Chan PF; Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.
  • Hamid RA; Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia. roslida@upm.edu.my.
Biometals ; 34(1): 141-160, 2021 02.
Article em En | MEDLINE | ID: mdl-33196940
Based on the recent studies depicting the potential of heterometallic gold complexes as potent antiproliferative agents, herein we first reported the preliminary mechanistic data on the in-vitro antiproliferative activity of tricyclohexylphosphanegold(I) n-mercaptobenzoate, Cy3PAu(n-MBA) where n = 2 (1), 3 (2) and 4 (3), and MBA = mercaptobenzoic acid, treated using MCF-7 breast cancer and A2780 ovarian cancer cells, respectively. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to assess the cytotoxicity of both cancer cells treated with 1-3, respectively. The IC50 of 1-3 were applied to the subsequent assays including cell invasion and thioredoxin reductase (TrxR) as well as ubiquitin activities specifically on Lys48 and Lys63-linked polyubiquitin chains via flowcytometric analysis. The mechanistic effect of 1-3 towards both cells were evaluated on human p53 signaling gene expressions via RT2 profiler Polymerase Chain Reductase (PCR) array. 1-3 were found to be highly cytotoxic towards both MCF-7 and A2780 cancer cell lines with the compounds were more sensitive towards the latter cells. 1-3 also suppressed TrxR and cell invasion activities by modulating p53 related genes related with proliferation, invasion and TrxR activities i.e. CCNB1, TP53, CDK4 etc. 1-3 also regulated Lys48 and Lys63-linked polyubiquitination by reactivation of p53, suggesting the ability of this gene in regulating inhibition of cytoskeletal reorganization via epithelial-mesenchymal transition (EMT), required for tumor progression. Taken together, the overall findings denoted that 1-3 exerted potent antiproliferative activity in MCF-7 and A2780 cells via activation of the p53 signaling pathway.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Compostos Organoáuricos / Antineoplásicos Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Compostos Organoáuricos / Antineoplásicos Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article