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An Oxygen-Chelate Complex, Palladium Bis-Acetylacetonate, Induces Apoptosis in H460 Cells via Endoplasmic Reticulum Stress Pathway Rather Than Interacting With DNA

An Oxygen-Chelate Complex, Palladium Bis-Acetylacetonate, Induces Apoptosis in H460 Cells via Endoplasmic Reticulum Stress Pathway Rather Than Interacting With DNA

Yi Wang, Jie Hu, Yuepiao Cai, Shanmei Xu, Bixia Weng, Kesong Peng, Xiaoyan Wei, Tao Wei, Huiping Zhou, Xiaokun Li, Guang Liang

J Med Chem. 2013 Dec 12;56(23):9601-11.

PMID: 24274598

Abstract:

Current precious-metal-containing anticancer agents are mostly chelated with N-containing ligands and function by interacting with DNA. In the present study, Pd(acac)2, a Pd(II) complex containing four O-donor ligands, has been evaluated as an active anticancer agent. Pd(acac)2 showed no interaction with N-ligand-containing DNA and the S-ligand-containing DMSO, probably because of the two six-member chelate rings that limit the release of the central Pd nuclei to bind to other ligands. Importantly, we found that Pd(acac)2 exhibited better growth inhibitory effects than cisplatin in several cancer cells. Treatment with Pd(acac)2 significantly induced apoptosis in H460 cells. Mechanistically, Pd(acac)2 induced the activation of a series of key components in ER stress-mediated apoptotic pathway, followed by caspase cleavage and activation, while cisplatin showed no similar effects. CHOP knockdown by specific siRNA significantly attenuated Pd(acac)2-induced cell apoptosis. Finally, Pd(acac)2 significantly inhibits H460 cell growth in xenograft mouse models. Taken together, these mechanistic insights on Pd(acac)2 provide us with a novel mechanism and strategy for the development of precious-metal-based anticancer drugs.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP14024614	Palladium(II) acetylacetonate		14024-61-4	Price

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