An Oxygen‐chelate Precious Metal‐based Complex, Palladium bis‐Acetylacetonate, Induces Apoptosis in Lung Cancer H460 cells via Endoplasmic Reticulum Stress Pathway rather than interacting with DNA

Abstract

Although some of palladium (Pd) complexes possess promising anti‐tumor activities, they are all chelated with N‐containing ligands and function by interacting with DNA. Few studies on the bio‐activities and mechanism of Pd‐O chelates have been conducted. In this study, a Pd complex containing four O‐donor ligands, Pd(acac)2, has been synthesized and evaluated as an anticancer agent. Solution stability test through 1H‐NMR spectra reveals that Pd(acac)2 maintained chemical stability being in the S‐donor containing DMSO solution. MTT assay shows that Pd(acac)2 exhibited significant cytotoxicity against BGC 823, HL‐60, KB, LS‐174T, and Hela cells. Flow cytometric assay reveals that treatment with Pd(acac)2 significantly induced apoptosis in H460 cells. Interestingly, gel electrophoresis and ultraviolet absorption assay show that Pd(acac)2 did not act directly on DNA. Immunoblotting assay indicates that the anti‐tumor effects of Pd(acac)2 are associated with ER stress‐mediated apoptosis pathway, followed by caspase activation. CHOP knockdown by specific siRNA significantly attenuated Pd(acac)2‐induced cell apoptosis, indicating that the apoptotic pathway is partly ER stress‐dependent. In summary, these data may provide us a novel mechanistic strategy for the development of metal‐based anticancer drugs.This work was supported by National Natural Science Funding of China (81102452).