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Cytotoxicity of bismuth(III) dithiocarbamate derivatives by promoting a mitochondrial-dependent apoptotic pathway and suppressing MCF-7 breast adenocarcinoma cell invasion

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Abstract

We previously reported that the bismuth(III) dithiocarbamate derivative, bismuth diethyldithiocarbamate (1) exhibited greater cytotoxicity while inducing apoptosis via the intrinsic pathway in MCF-7 cells. We further evaluated the other bismuth(III) dithiocarbamate derivatives, Bi[S2CNR]3, with R = (CH2CH2OH)(iPr), (CH2)4, and (CH2CH2OH)(CH3), denoted as 2, 3, and 4, respectively, in the same MCF-7 cell line. 2–4 were found to exhibit IC50 values of 10.33 ± 0.06 µM, 1.07 ± 0.01 µM and 25.37 ± 0.12 µM, respectively, compared to that of cisplatin at 30.53 ± 0.23 µM. Apoptotic promotion via the mitochondrial-dependent pathway was due to the elevation of intracellular reactive oxygen species (ROS), promotion of caspases, release of cytochrome c, fragmentation of DNA, and results of staining assay observed in all compound-treated cells. 2–4 are also capable of suppressing MCF-7 cell invasion and modulate Lys-48 also Lys-63 linked polyubiquitination, leading to proteasomal degradation. Analysis of gene expression via qRT-PCR revealed their modulation, which supported all activities conducted upon treatment with 2–4. Altogether, bismuth dithiocarbamate derivatives, with bismuth(III) as the metal center bound to ligands, isopropyl ethanol, pyrrolidine, and methyl ethanol dithiocarbamate, are potential anti-breast cancer agents that induce apoptosis and suppress metastasis. Further studies using other breast cancer cell lines and in vivo studies are recommended to clarify the anticancer effects of these compounds.

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Acknowledgements

The authors thanked Prof Edward R.T. Tiekink for providing the sample and Universiti Malaya for providing the grants under High Impact Research Schemes and collaborated with us by providing the compounds and the funding. The authors also thanked Prof Dr Noor Saadah Abd Rahman, the Deputy Vice Chancellor (Research and Innovation) at the University of Malaya for giving us the consent to publish the data

Funding

This research was funded by the Ministry of Higher Education, Malaysia (grant numbers UM.C/HIR-MOHE/SC/03 and UM.C/HIR-MOHE/SC/12).

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Authors and Affiliations

  1. Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia

    Pit Foong Chan, Kok Pian Ang & Roslida Abd Hamid

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Contributions

Conceptualization, RAH; methodology, RAH; validation, CPF and RAH; formal analysis, CPF and AKP; investigation, CPF and AKP; data curation, CPF and AKP; writing—original draft preparation, CPF; writing—review and editing, RAH; visualization, CPF and AKP; supervision, RAH; project administration, RAH All authors have read and agreed to the published version of the manuscript.

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Correspondence to Roslida Abd Hamid.

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Chan, P.F., Ang, K.P. & Hamid, R.A. Cytotoxicity of bismuth(III) dithiocarbamate derivatives by promoting a mitochondrial-dependent apoptotic pathway and suppressing MCF-7 breast adenocarcinoma cell invasion. J Biol Inorg Chem (2024). https://doi.org/10.1007/s00775-023-02041-x

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