It is a worrying fact that chemotherapeutic options for treating triple negative breast cancer are limited in nature, including cisplatin, which has been reported to have various side effects during chemotherapeutic treatment on the patient. Based on those issues, it has been reported by our research group and others that cobalt-containing complexes have shown great potential in anti-cancer properties when compared to cisplatin. In this study, a cobalt(III) complex with 1,10-phenanthroline and 9-anthraldehyde-N(4)-methylthiosemicarbazone as ligands was utilised in vitro studies, along with its use in agarose gel electrophoresis to assess its DNA cleaving efficacy.

In vitro studies were carried out on cancer MDA-MB-231 VIM RFP and non-cancer MCF-10A cell lines by using the CCK-8 viability assay. Caspase 3/7 and reactive oxygen species (ROS) activities were also assessed by carried out by using flow cytometry, caspases 1 and 9 via luminescence assays. Studies involving mitochondrial function were carried out by using a Seahorse Analyzer.

From the agarose gel electrophoresis study, the cobalt(III) complex showed a significant increase in the amount of relaxed DNA after 24 h of incubation. From the data acquired via in vitro studies, the cobalt(III) complex showed a lower IC₅₀ value in cancer cells (17.59 μM) when compared to non-cancer cells (61.26 μM). The IC₅₀ values with the control, cisplatin, were 22.17 μM and 31.87 μM for the cancer and non-cancer cells, respectively.

It was also found that caspase 3/7 and ROS were activated at 2 h of treatment with the IC₅₀ value of the complex; while caspase 1 was at 4 h, which indicated the coordinated activation of pyroptosis and apoptosis in the cell death of the breast cancer cell line.

The complex also caused mitochondrial dysfunction and activation of caspase 9, which indicated the induction of intrinsic apoptotic cell death. Thus, the complex induced cell death in the breast cancer cell line via activation of oxidative stress which activated pyroptosis and apoptosis.

Brittney Anderson

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