Immunogenicity and cytotoxicity of a platinum(IV) complex derived from capsaicin

Dalton Trans. 2021 Mar 16;50(10):3516-3522. doi: 10.1039/d0dt03470c.

Abstract

Platinum-based anticancer drugs constitute the cornerstone of chemotherapy for various cancers. Although cytotoxic agents are considered to have immunosuppressive effects, increasing evidence suggests that some cytotoxic compounds can effectively stimulate the antitumor immune response by inducing a special type of apoptosis called immunogenic cell death (ICD). A platinum(iv) complex (DCP) modified with the derivative of synthetic capsaicin (nonivamide) was designed to elicit ICD. The complex exhibited high cytotoxicity against a panel of human cancer cell lines including pancreas (PANC-1), breast (MCF-7), and liver (HepG2) cancer cells, and osteosarcoma (MG-63) cells. In addition to causing DNA damage, DCP also triggered the translocation of calreticulin (CRT) as well as the release of ATP and HMGB1 protein in PANC-1 cells, thus manifesting an efficient ICD-inducing effect on cancer cells. Furthermore, the DCP-treated PANC-1 cell-conditioned culture medium promoted the release of IFN-γ and TNF-α to induce the immune response of human peripheral blood mononuclear cells, thereby increasing their cytotoxicity to cancer cells. Concurrently, the phagocytosis of PANC-1 cells by macrophages was also augmented by DCP. The results demonstrate that DCP is an effective inducer of ICD and a potential agent for chemoimmunotherapy of cancers.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Capsaicin / chemical synthesis
  • Capsaicin / chemistry
  • Capsaicin / pharmacology*
  • Cattle
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • DNA / chemistry
  • DNA / drug effects
  • DNA Damage
  • Drug Screening Assays, Antitumor
  • Humans
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / immunology
  • Molecular Structure
  • Photosensitizing Agents / chemical synthesis
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology*

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Photosensitizing Agents
  • DNA
  • calf thymus DNA
  • Capsaicin