lignans and cobaltous-chloride

Angiogenesis has a key role in the tumor progression and metastasis; targeting endothelial cell proliferation has emerged as a promising therapeutic strategy for the prevention of cancer. Previous studies have revealed a complex association between the process of angiogenesis and autophagy and its outcome on tumorigenesis. Autophagy, also known as type-II cell death, has been identified as an alternative way of cell killing in apoptotic-resistant cancer cells. However, its involvement in chemoresistance and tumor promotion is also well known. In this study, we used a derivate of natural product magnolol (Ery5), a potent autophagy inducer, to study the association between the autophagy and angiogenesis in both in vitro and in vivo model system. We found that the robust autophagy triggered by Ery5, inhibited angiogenesis and caused cell death independent of the apoptosis in human umbilical cord vein endothelial cells and PC-3 cells. Ery5 induced autophagy effectively inhibited cell proliferation, migration, invasion and tube formation. We further demonstrated that Ery5-mediated autophagy and subsequent inhibition of angiogenesis was reversed when autophagy was inhibited through 3-methyl adenine and knocking down of key autophagy proteins ATG7 and microtubule-associated protein light chain 3. While evaluating the negative regulation of autophagy on angiogenesis, it was interesting to find that angiogenic environment produced by the treatment of VEGF and CoCl2 remarkably downregulated the autophagy and autophagic cell death induced by Ery5. These studies, while disclosing the vital role of autophagy in the regulation of angiogenesis, also suggest that the potent modulators of autophagy can lead to the development of effective therapeutics in apoptosis-resistant cancer.

Topics: Animals; Autophagy; Biphenyl Compounds; Cell Cycle; Cell Death; Cell Line; Cell Proliferation; Cobalt; Human Umbilical Vein Endothelial Cells; Humans; Lignans; Microtubule-Associated Proteins; Neovascularization, Pathologic; Phenols; Rats; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2

Two new tetrahydrofuran lignans, schiglaucin A and B (1-2), together with eight known analogues (3-10), were isolated from the stems of Schisandra glaucescens Diels. Their structures were elucidated on the basis of spectroscopic techniques (HRESIMS, UV, IR, NMR, and CD experiments). All of the compounds were tested for their neuroprotective activities against H₂O₂- and CoCl₂-induced cell injuries in SH-SY5Y cells, respectively. Compounds 1-10 showed significant neuroprotective effects against H₂O₂-induced SH-SY5Y cell death, while compounds 1-5 and 8-10 exhibited significant neuroprotective effects against CoCl₂-induced SH-SY5Y cell injury.

Topics: Cell Death; Cell Survival; Cobalt; Humans; Hydrogen Peroxide; Lignans; Molecular Structure; Neuroblastoma; Neuroprotective Agents; Plant Extracts; Plant Stems; Schisandra; Tumor Cells, Cultured

Hypoxia-inducible factor-1α (HIF-1α) plays a pivotal role in the reaction of a tumour to hypoxia. In this study, we examined the inhibitory effect of a natural compound, honokiol, on HIF-1α activity and tumour growth in combination with radiation.. The inhibitory effect of honokiol on hypoxia-responsive element (HRE) controlled luciferase activity and HIF-1α accumulations stimulated by CoCl(2), or hypoxia was examined. Effect of honokiol on HIF-1α levels within hypoxic tumour microenvironment was investigated by immunohistochemical and in vivo bioluminescent studies. The in vivo radiosensitising activity of honokiol was evaluated with subcutaneous murine colon carcinoma, CT26, xenografts of BALB/c mice treated with honokiol, radiation, or both.. Suppression of luciferase (luc) activity in HRE-luc stable cells by honokiol was in agreement with the results of decreased HIF-1α accumulation. In CT26-HRE-luc tumour-bearing mice, the inhibitory effect of intraperitoneally injected honokiol on HIF-1α-regulated luciferase activities induced by either CoCl(2) or radiation could be monitored non-invasively. Lastly, honokiol in combination with irradiation produced synergistic delay of CT26 tumour growth.. Our data suggest that honokiol can exert its anticancer activity as a HIF-1α inhibitor by reducing HIF-1α protein level and suppressing the hypoxia-related signaling pathway. The animal experiment indicates that honokiol improves the therapeutic efficacy of radiation.

Topics: Animals; Antineoplastic Agents, Phytogenic; Biphenyl Compounds; Cobalt; Enzyme-Linked Immunosorbent Assay; Female; HeLa Cells; Humans; Hypoxia; Hypoxia-Inducible Factor 1; Immunohistochemistry; Lignans; Luciferases; Melanoma, Experimental; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neoplasm Transplantation; Neoplasms