ABSTRACT
Angiogenesis is the process of new vessel formation from pre-existing blood vasculature and is critical for continuous tumor growth. We previously reported that an ethanolic extract of Gleditsia sinensis thorns (EEGS) and its active constituent, cytochalasin H, have anti-angiogenic activity in vitro and in vivo via suppression of endothelial cell functions. In the present study, EEGS and cytochalasin H were observed to efficiently inhibit tumor growth in an in ovo xenograft model without significant toxicity. We repeatedly observed the anti-tumor and anti-metastatic effects of EEGS in representative animal models. These results suggest that EEGS and its active constituent, cytochalasin H, are potential candidates for the development of anti-angiogenic cancer drugs.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Antineoplastic Agents, Phytogenic/therapeutic use , Cytochalasins/therapeutic use , Gleditsia/chemistry , Phytotherapy , Plant Extracts/therapeutic use , Angiogenesis Inhibitors/pharmacology , Animals , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , Chick Embryo , Cytochalasins/pharmacology , Humans , Mice, Inbred BALB C , Mice, Inbred C57BL , Neovascularization, Pathologic/drug therapy , Plant Epidermis , Plant Extracts/pharmacologyABSTRACT
Two new cytochalasans, trichalasins C (1) and D (2) together with known cytochalasans aspochalasins D (3), M (4) and P (5) were isolated from one endophytic fungus Trichoderma gamsii inhabiting in traditional medicinal plant Panax notoginseng (BurK.) F.H.Chen. The structures for the new compounds 1 and 2 were determined by NMR and HRESIMS, and their relative configurations were established by analysis of coupling constants and NOESY correlations. Compound 3 displaying inhibitory activity with EC50 value 5.72 µM, whereas the EC50 values for compounds 1, 2 and 4, 5 are more than 40 µM.
Subject(s)
Biological Products/chemistry , Cytochalasins/isolation & purification , Panax notoginseng/microbiology , Trichoderma/chemistry , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Biological Products/pharmacology , Biological Products/therapeutic use , Cytochalasins/pharmacology , Cytochalasins/therapeutic use , Endophytes/chemistry , Female , HeLa Cells , Humans , Molecular Structure , Uterine Cervical Neoplasms/drug therapyABSTRACT
Two new lactones, 1 and 2, together with five known compounds, 3-7, were isolated from the marine mangrove fungus Xylaria sp. BL321. Their structures were determined by comprehensive analysis of their MS and NMR spectroscopic data. The absolute configurations of 1 and 2 were established on the basis of electronic circular dichroism calculations. It was found that the exocyclic double bond of 1 rearranged into a cyclic double bond to form a new crystal compound (1a) in diluted NaOH solution. Compound 3 was isolated for the first time as a natural product; its absolute configuration was determined by single-crystal X-ray crystallography. Compounds 4-7 displayed cytotoxicity against human breast cancer cell lines MCF-7 and MDA-MB-435, while compounds 1- 3 were inactive (IC(50) > 50 µM).