Elemene (ELE), a natural plant drug extracted from Curcumae Rhizoma, has been widely used for cancer treatment in China for more than 20 years. Although it is reported to be a broad-spectrum anticancer drug, the mechanism underlying the action of ELE in the treatment of breast cancer remains to be fully elucidated. Heparanase, a mammalian endo-D-glucuronidase, is involved in degradation of the extracellular matrix (ECM), and thus promotes tumor progression and metastasis. The downregulation of heparanase can effectively reduce tumor malignant behaviors. In the present study, the inhibitory effects of ELE were evaluated in breast cancer cells using a Cell Counting kit 8 assay. The migratory and invasive capabilities of cancer cells were investigated using a wound healing assay, real-time cell analysis and a Transwell assay. In addition, western blot analysis was used to assess alterations in the expression levels of key proteins. The present results confirmed the antiproliferative and antimetastatic effects of ELE, using low-molecular weight heparin (LMWH) as a positive control. In addition, ELE was demonstrated to downregulate the expression of heparanase, and decrease the phosphorylation of extracellular signal-regulated kinase and AKT. These findings suggested that ELE may be a promising agent targeting heparanase in the treatment of breast cancer.

Triple-negative breast cancer (TNBC), which is characterized by inherently aggressive behavior and lack of recognized molecular targets for therapy, poses a serious threat to women's health worldwide. However, targeted treatments have yet to be made available. A crosstalk between tumor cells and platelets (PLT) contributing to growth, angiogenesis and metastasis has been reported in numerous cancers. Heparanase (Hpa), the only mammalian endoglycosidase that cleaves heparan sulfate, has been demonstrated to contribute to the growth, angiogenesis and metastasis of numerous cancers. Hypoxia affects the growth, angiogenesis and metastasis of nearly all solid tumors, and the ability of Hpa to promote invasion is enhanced in hypoxia. However, whether Hpa can strengthen the crosstalk between tumor cells and PLT, and whether enhancing the biological function of Hpa in TNBC promotes malignant progression, have yet to be fully elucidated. The present study, based on bioinformatics analysis and experimental studies in vivo and in vitro, demonstrated that Hpa enhanced the crosstalk between TNBC cells and PLT to increase the supply of oxygen and nutrients, while also conferring tolerance of TNBC cells to oxygen and nutrient shortage, both of which are important for overcoming the stress of hypoxia and nutritional deprivation in the tumor microenvironment, thereby promoting malignant progression, including growth, angiogenesis and metastasis in TNBC. In addition, the hypoxia-inducible factor-1a (HIF-1a)/vascular endothelial growth factor-a (VEGF-a)/phosphorylated protein kinase B (p-)Akt axis may be the key pathway involved in the effects of Hpa on the biological processes mentioned above. Therefore, improving local hypoxia, anti-Hpa treatment and inhibiting PLT activation may improve the prognosis of TNBC.

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Three new complexes {[Cu(L 1 ) 2 (NO 3 ) 2 ]·H 2 O} ¥ (1), {[Cu 4 (L 2 ) 2 (OAc) 8 ]×CH 3 CH 2 OH} ¥ (2) and [Cd 2 (L 3 ) 3 (NO 3 ) 4 (H 2 O) 2 ] ¥ (3) (L 1 = 4-phenyl-7-(pyridine-3-yl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole, L 2 = 4-(pyridine-3-yl)-7-phenyl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole, and L 3 = 4-(pyridine-4-yl)-7-phenyl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole) have been synthesized and characterized by elemental analyses, IR spectra and single crystal X-ray diffraction. The structural analyses reveal that complex 1 is a neutral 2-D network structure with a 4 4 topology, 2 has a 1-D neutral coordination chain with a [Cu 2 (CH 3 COO) 4 ] dinuclear structural unit bridged by four acetate ions, and 3 is a neutral rhombohedral grid structure. All the complexes are air stable at room temperature. Furthermore, the fluorescent properties of complex 3 and corresponding ligand L 3 have been investigated and discussed. Scheme 1 The structure of ligands L 1 -L 3 Scheme 2 The route of synthesis of ligands L 1 -L 3 CHEMICAL SOCIETY Fig. 1. View of (a) the coordination environment of Cu II ions in 1. (b) 2-D (4,4) network structure of 1 (H atoms are omitted for clarity). (c) 4 4 topology of 1. 790 www.jccs.wiley-vch.de