Pt(II)-NHC Complex 2C

Pt(II)-NHC complex 2C is an inducer of immunogenic cell death (ICD) in cancer cells.¹ It selectively inhibits proliferation of HT-29, MCF-7, A2780, A549, HepG2, and Hepa 1-6 cancer cells (IC₅₀s = 2.78, 0.71, 0.99, 1.77, 0.33, and 0.36 µM, respectively) over non-cancerous L-02 liver cells (IC₅₀ = 3.02 µM). It induces the release of damage-associated molecular patterns (DAMPs) associated with ICD in Hepa 1-6 cells by increasing calreticulin (CRT) exposure on the cell membrane, extracellular ATP release, and high mobility group protein B₁ (HMGB1) translocation to the cytoplasm. Pt(II)-NHC complex 2C (2 µM) also increases the generation of reactive oxygen species (ROS), as well as induces DNA damage and cell cycle arrest at the S phase in HepG2 cells. It reduces tumor growth in a mouse antitumor vaccination model of the ICD response in mice when used at a concentration of 5 µM in Hepa 1-6 cells prior to implantation.

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1. Bian, M., Fan, R., Yang, Z., et al. Pt(II)-NHC complex induces ROS-ERS-related DAMP balance to harness immunogenic cell death in hepatocellular carcinoma. J. Med. Chem. 65(3), 1848-1866 (2022).