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Abstract: Bigelovin is a sesquiterpene lactone isolated from the plant Inula helianthus-aquatica which was traditionally used in cancer treatment in Yunnan, China. The potent apoptotic activities of bigelovin in human leukemia U937 cells were shown in our previous study. The present study investigated the anti-angiogenic and immunomodulatory effects of bigelovin using transgenic zebrafish Tg(fli1a:EGFP)y1 with fluorescent blood vessels and human peripheral blood mononuclear cells (PBMCs), respectively. Furthermore, the inhibitory activities of bigelovin on the human endothelial cell adhesion molecules (CAMs) were also examined. Our results showed that the growth of subintestinal vessels of the bigelovin-treated zebrafish embryos was significantly inhibited and the gene expressions in angiogenesis signaling pathways (e.g. Ang2 and Tie2) of the zebrafish were down-regulated after bigelovin treatment. Besides, the proliferation and Th1 cytokines productions (e.g. IFN-γ, IL-2 and IL-12) were suppressed in bigelovin-treated PBMCs. On the other hand, bigelovin was shown to significantly inhibit the human monocyte adhesion to human endothelial cells and the gene expressions of inflammation-related CAMs (e.g. ICAM-1, VCAM-1 and E-selectin) were significantly down-regulated in bigelovin-treated human endothelial cells. In summary, our data provide the first evidence that bigelovin possesses anti-angiogenic and immunomodulatory activities, suggesting bigelovin may exert multi-target functions against cancer in animal models. [Copyright &y& Elsevier]

Abstract: Several curcuminoids and sesquiterpenoids isolated from Curcuma longa (CL) have been shown to have many pharmacological activities. In the present study, the immunomodulatory activities of the polar fractions of CL hot water extracts were investigated using human peripheral blood mononuclear cells (PBMC). Our results showed that the high polarity fraction of the hot water extract exhibited stimulatory effects on PBMC proliferation as shown in [methyl-3H]-thymidine incorporation assay. In an attempt to isolate the active components responsible for the activities, further partition with ethyl acetate, n-butanol and ethanol, progressively were performed. The cytokine productions (TGF-β, TNF-α, GM-CSF, IL-1α, IL-5, IL-6, IL-8, IL-10, IL-13, etc.) have been modulated by a polysaccharide-enriched fraction as shown in ELISA and cytokine protein array. The proportion of CD14 positive stained PBMC was increased by such fraction. The composition of monosaccharide of the active fraction has been determined by GC–MS and gel permeation chromatography. The immunostimulatory effects of C. longa polysaccharides on PBMC were shown for the first time. The findings revealed the potential use of C. longa crude extract (containing curcuminoids and polysaccharides) as an adjuvant supplement for cancer patients, whose immune activities were suppressed during chemotherapies. [ABSTRACT FROM AUTHOR]

Abstract: The rhizome of Curcuma longa (CL) has been commonly used in Asia as a potential candidate for the treatment of different diseases, including inflammatory disorders and cancers. The present study evaluated the anti-proliferative activities of the isolated compounds (three curcuminoids and two turmerones) from CL, using human cancer cell lines HepG2, MCF-7 and MDA-MB-231. The immunomodulatory activities of turmerones (α and aromatic) isolated from CL were also examined using human peripheral blood mononuclear cells (PBMC). Our results showed that the curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin) and α-turmerone significantly inhibited proliferation of cancer cells in dose-dependent manner. The IC50 values of these compounds in cancer cells ranged from 11.0 to 41.8μg/ml. α-Turmerone induced MDA-MB-231 cells to undergo apoptosis, which was confirmed by annexin-V and propidium iodide staining, and DNA fragmentation assay. The caspase cascade was activated as shown by a significant decrease of procaspases-3, -8 and -9 in α-turmerone treated cells. Both α-turmerone and aromatic-turmerone showed stimulatory effects on PBMC proliferation and cytokine production. The anti-proliferative effect of α-turmerone and immunomodulatory activities of ar-turmerone was shown for the first time. The findings revealed the potential use of CL crude extract (containing curcuminoids and volatile oil including turmerones) as chemopreventive agent. [Copyright &y& Elsevier]

Highlights: [•] Metronomic ZOL on tumor growth and osteolysis in breast cancer mice were studied. [•] Metronomic ZOL (zoledronic acid) resulted in a significant reduction of tumor burden. [•] Metronomic ZOL did not promote lung or liver metastasis. [•] Metronomic ZOL protected the bone from breast cancer-induced osteolysis. [•] This dosing schedule of ZOL showed great potential against metastatic breast cancer. [Copyright &y& Elsevier]