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Updated: May 30, 2025

Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents
Published on: May 28, 2014
Platinum(IV) Complexes Trigger Death Receptors and Natural Killer Cells to Suppress Breast Cancer
Linxiang Cai1, Hanhua Chen2, Ying Wang2
1State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. China.
Abstract:
Chemoimmunotherapy is an alternative treatment against cancers. Platinum(IV) complexes FMP and DFMP, coupling formononetin derivative as axial ligand(s), were designed to suppress triple-negative breast cancer (TNBC) by activating death receptors (DRs) and natural killer (NK) cells. These complexes show great potential to overcome the resistance of TNBC to chemotherapy by inducing both intrinsic and extrinsic apoptosis in cancer cells. Particularly, FMP with one axial formononetin derivative not only induced the caspase-3-dependent intrinsic apoptosis but also upregulated the expression of DRs and caspase-8, triggered the extrinsic apoptosis, and enhanced the cytotoxic ability of NK92 cells. Moreover, FMP increased the release of granzyme B, restrained the proliferation and differentiation of myeloid-derived suppressor cells, and the secretion of IL-10, thus inhibiting the TNBC in vitro and in vivo. The results demonstrate that FMP overcomes the chemoresistance and immune escape of TNBC through a new mechanism involving the synergy of chemotherapy and immunotherapy.
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