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Three new dinuclear Co(II) complexes [Co2(L1)2Cl2](PF6)2 (1), [Co2L2(OAc)2(CH3OH)4](ClO4)2 (2), and [Co2L3(OAc)2(CH3OH)4](ClO4)2 (3) were synthesized and structurally determined by X‐ray single‐crystal diffraction analysis as well as IR, elemental analysis, and mass spectrometry. All complexes exhibit efficiently self‐activated cleavage activity with hydrolytic mechanism, which was accurately proved by addition of regular radical scavengers, anaerobic cleavage experiment, and 2‐thiobarbituric acid reaction. Complex 1 exhibited higher selective cytotoxicity against tumor cells than normal cells, which is significantly better than that of cisplatin. Hoechst 33342 staining, intracellular ROS generation and mitochondrial membrane potential were conducted to assess the apoptosis‐inducing activity of 1. The effect of complex 1 on cell invasion was observed by Transwell assay and angiogenesis experiment, and the results demonstrated that 1 could inhibit the cell invasion and angiogenesis. [ABSTRACT FROM AUTHOR]

Lymph node metastasis (LNM) is associated with poor survival in patients with Head and Neck cancer (HNC). Aryl hydrocarbon receptor repressor (AHRR) is thought to be responsible for increased lymphangiogenesis and LNM. AHRR and endothelial PAS domain-containing protein 1 (EPAS1) are basic helix-loop-helix/per-arnt-sim family transcription factors, however, its central role in lymphangiogenesis remains to be explored. In this study, we explored that EPAS1 dimerizes with HIF-1β during lymphangiogenes and tumor growth, inducing expression of many genes, including vascular endothelial growth factor-d (VEGFD). AHRR wild-type ( Ahrr +/+ ) transgenic carcinoma of the mice develop tumors with greater frequency than AHRR-null ( Ahrr -/- ) mice, even though prevalence of squamous epithelial hyperplasia is not inhibited. Hypoxia induced VEGFD protein in a genotype-dependent fashion in Ahrr +/+ , Ahrr +/- and Ahrr -/- HNC. However, hypoxia induced upstream proteins in the phosphatidylinositol 3-kinase-signaling cascade to a similar extent in HNC of each Ahrr genotype, evidenced by Akt phosphorylation. These findings suggest that AHRR induces HIF-1β expression, increasing interaction with EPAS1 enhancing VEGFD production and lymphangiogenesis in HNC., Competing Interests: None., (AJCR Copyright © 2022.)