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A bismuth diethyldithiocarbamate compound induced apoptosis via mitochondria-dependent pathway and suppressed invasion in MCF-7 breast cancer cells.
Chan, Pit Foong; Ang, Kok Pian; Hamid, Roslida Abd.
Afiliação
  • Chan PF; Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.
  • Ang KP; 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(2): 365-391, 2021 04.
Article em En | MEDLINE | ID: mdl-33555494
Interest in bismuth(III) dithiocarbamate complexes as potential drug candidates is increasing due to their low toxicity compared to other group 15 elements (pnictogen) of the periodic table. Bismuth dithiocarbamate compounds have been reported to induce greater cytotoxicity in various human carcinoma cancer cell lines. Using various in vitro cancer-related assays, we investigated the antiproliferative activity of bismuth diethyldithiocarbamate, denoted as 1, against the MCF-7 human breast adenocarcinoma cell line and the effect on genes that may be involved in antiproliferation, apoptosis, DNA fragmentation, invasion and polyubiquitination functions. In general, 1 exhibited high cytotoxicity in MCF-7 cells, with an IC50 of 1.26 ± 0.02 µM, by inducing the intrinsic apoptotic pathway, as ascertained by measurements of intracellular reactive oxygen species (ROS), caspase activity, the amount of cytochrome c released and the extent of DNA fragmentation and by staining assays that reveal apoptotic cells. In addition, 1 significantly attenuated cell invasion and modulated several cancer-related genes, including PLK2, FIGF, FLT4, PARP4, and HDAC11, as determined via gene expression analysis. The NF-κB signaling pathway was inhibited by 1 upon the activation of Lys48- and Lys63-linked polyubiquitination, thus leading to its degradation via the proteasome. Overall, 1 has the potential to act as an antiproliferative agent and a proteasome inhibitor in estrogen-positive breast cancer.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Bismuto / Apoptose / Ditiocarb / Complexos de Coordenação / Mitocôndrias / Antineoplásicos Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Bismuto / Apoptose / Ditiocarb / Complexos de Coordenação / Mitocôndrias / Antineoplásicos Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article