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Pt(IV) hybrids containing a TDO inhibitor serve as potential anticancer immunomodulators

Shixian Hua1, Feihong Chen2, Xinyi Wang1

  • 1Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China.

Journal of Inorganic Biochemistry
|April 6, 2019
PubMed

Tryptophan 2,3-dioxygenase (TDO), an immunosuppressive enzyme, can involve in immune evasion and tumor tolerance. TDO inhibitors can boost the efficacy of chemotherapeutics by promoting immunity. Herein, a strategy to introduce a TDO inhibitor into Pt(IV) complexes for reversing tumor immune suppression was adopted. A mono-modified Pt(IV) complex, 3, displayed significant antitumor activity against human liver cancer cells. Flow cytometry study revealed that complex 3 could induce cell death via a mitochondrial-dependent apoptosis pathway and arrest the cell cycle at S phase. Furthermore, complex 3 was effective to enhance T-cell immune responses by inhibiting the TDO enzyme expression to block the kynurenine production and inactivating the downstream of aryl hydrocarbon receptor (AHR).

Keywords:
AntitumorImmuno-chemotherapyImmunomodulatorPlatinum(IV) hybridsTryptophan 2,3-dioxygenase

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