A significantly non-toxic novel Cobalt(III) Schiff base complex induces apoptosis via G2-M cell cycle arrest in human breast cancer cell line MCF-7

Aims: Metal complexes have ignited considerable interest in the field of chemotherapy after the serendipitous discovery of cisplatin but the severe toxicity of these platinum-based drugs compelled researchers to search for newer, more effective lesser toxic anticancer drugs. Materials and methods: Structural analysis is done by different physicochemical techniques including X-ray single crystallography. Toxicity study has been done in normal Swiss albino mice. MTT assay assessed cell viability. Apoptosis, cell cycle arrest, and cell proliferation were assessed by FACS using Annexin V-PI, PI, and CFSE staining respectively. Western blot quantifies protein expression. While cell migration was studied by wound healing assay. Key findings: One-pot synthesis of a novel mononuclear cobalt(III)-Schiff base complex (1) (> 99 % purity) and its complete characterization have been done. Cell viability assay showed that 1 (IC50 = 16.81 +/- 1.33 mu M) exhibits cytotoxicity at much lower concentration in comparison to oxaliplatin (IC50 = 31.4 +/- 0.69 mu M) against MCF-7 cells for 24 h of therapy without being overly toxic to human PBMCs (IC50 >= 60 mu M). Additional in vitro studies demonstrated that 1 induces apoptosis via G2-M cell cycle arrest and reduces cell proliferation as well as cell migration in MCF-7 cells. In vivo subacute toxicity (28 days) and systemic chronic toxicity (40 days) studies were carried out in normal Swiss albino mice showed 1 is significantly nontoxic to the host. Significance: The readily synthesizable, significantly nontoxic cobalt complex with appreciable anticancer activity implies that it might be an effective chemotherapeutic agent for new-age anti-tumor medication.

Automated summary

A novel cobalt complex 1 exhibits significant anticancer activity with lower toxicity compared to oxaliplatin against MCF-7 cells, and shows no significant toxicity to the host. This complex has the potential to be a new chemotherapeutic agent for anti-tumor medication.