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Cytotoxic cobalt (III) Schiff base complexes: in vitro anti-proliferative, oxidative stress and gene expression studies in human breast and lung cancer cells

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Abstract

Increasing cancer drug chemo-resistance, especially in the treatment of breast and lung cancers, alarms the immediate need of newer and effective anticancer drugs. Until now, chemotherapeutics based on metal complexes are considered the most effective treatment modality. In the present study, we have evaluated the cytotoxic effect of two cobalt (III) Schiff base complexes based on the leads from complex combinatorial chemistry. Cobalt (III) Schiff base complexes (Complex 3 = Co(Ph-acacen)(HA)2](ClO4) and Complex 4 =  [Co(Ph-acacen)(DA)2](ClO4)] (Ph-acacen, 1-phenylbutane-1,3-dione; DA, dodecyl amine; HA, heptylamine) were evaluated against human breast cancer cell MCF-7 and lung cancer cell A549 using MTT cell viability assay, cellular morphological changes studied by Acridine Orange and Ethidium Bromide (AO/EB), Dual fluorescent staining, Hoechst staining 33248, Comet assay, Annexin V-Cy3 and 6 CFDA assay, JC-1 staining, Reactive oxygen species (ROS) assay, Immunofluorescence assay, and Real-time reverse transcription-polymerase chain reaction (RT-qPCR). Treatment of cobalt (III) Schiff base complexes (Complex 3 & 4) affected the viability of the cancer cells. The cell death induced by the complexes was predominantly apoptosis, but necrosis also occurred to a certain extent. Complex 4 produced better cytotoxic effect than complex 3, and MCF-7 cell was more responsive than A549. In that order, the complexes were more selective to cancer cell than normal cell, and more effective in overall performance than the standard drug cisplatin. Therefore, we conclude that cobalt (III) Schiff base complexes, especially complex 4, have the potential to be developed as effective drugs for treatment of cancers in general, and breast and lung cancers in particular.

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(Adopted from Manojkumar et al. 2019)

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Acknowledgements

We express our sincere gratitude to the Dr. R. Thirumurugan, Co-ordinator of National Centre for Alternatives to Animal Experiments (NCAAE), for the continuous support, encouragement, and guidance during the course of this research. This work was financially supported by National Centre for Alternatives to Animal Experiments (NCAAE) under UGC-CPEPA scheme, Government of India (F.No.2-1/2013 (NS/PE)). The research facility provided by Mahatma Gandhi-Doerenkamp Centre, established by Doerenkamp-Zbinden Foundation, and the Department of Science and Technology, Government of India, under DST-Promotion of University Research and Scientific Excellence (PURSE) scheme-Phase II, Rashtriya Uchchatar Shiksha Abhiyan (RUSA)-2.O by the Department of Animal Science is heartily acknowledged. The authors thank the Management of Bishop Heber College (Autonomous), Tiruchirappalli-620 017, Tamil Nadu, India, for the support (F.No: MRP/1014/2020 dated : 23.12.2020) and facilities provided through Material Chemistry Lab, PG and Research Department of Chemistry and DST-FIST Instrumentation Centre (HAIF) at Bishop Heber College.

Funding

University Grants Commission, F.No.2-1/2013 (NS/PE), Balakrishnan Gowdhami, National Centre for Alternatives to Animal Experiments (NCAAE) under UGC-CPEPA scheme, Balakrishnan Gowdhami, Department of Science and Technology, Ministry of Science and Technology, Mahatma Gandhi-Doerenkamp Centre, Mohammad Abdulkader Akbarsha,University Research, Balamuthu Kadalmani, Scientific Excellence (PURSE) scheme-Phase II, Balamuthu Kadalmani, Rashtriya Uchchatar Shiksha Abhiyan (RUSA)-2.O, Balamuthu Kadalmani, Doerenkamp-Zbinden Foundation, Mahatma Gandhi-Doerenkamp Centre, Mohammad Abdulkader Akbarsha.s

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Authors and Affiliations

  1. Department of Animal Science, Bharathidasan University, Tiruchirappalli, Tamilnadu, 620024, India

    Balakrishnan Gowdhami, Venkatesan Ramya & Balamuthu Kadalmani

  2. National Centre for Alternatives to Animal Experiments, Bharathidasan University, Tiruchirappalli, Tamilnadu, 620024, India

    Balakrishnan Gowdhami & Balakrishnan Karthiyayini

  3. Department of Chemistry, Bishop Heber College, Tiruchirappalli, Tamilnadu, India

    Yesaiyan Manojkumar

  4. Department of Biotechnology, Bharathidasan University, Tiruchirappalli, Tamilnadu, 620024, India

    R. T. V. Vimala

  5. Department of Microbiology, Bharathidasan University, Tiruchirappalli, Tamilnadu, 620024, India

    Balakrishnan Karthiyayini

  6. Mahatma Gandhi-Doerenkamp Centre for Alternatives, Bharathidasan University, Tiruchirappalli, Tamilnadu, 620024, India

    Mohammad Abdulkader Akbarsha

  7. Department of Biotechnology & Research Coordinator, National College (Autonomous), Tiruchirappalli, Tamilnadu, 620001, India

    Mohammad Abdulkader Akbarsha

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  1. Balakrishnan Gowdhami
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Gowdhami, B., Manojkumar, Y., Vimala, R.T.V. et al. Cytotoxic cobalt (III) Schiff base complexes: in vitro anti-proliferative, oxidative stress and gene expression studies in human breast and lung cancer cells. Biometals 35, 67–85 (2022). https://doi.org/10.1007/s10534-021-00351-8

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