Background: Daphne Mucronata extract has a decreasing effect on the size of breast adenocarcinoma in rats. So in this study, the effect of Daphne Mucronata purified diterpene were investigated on co culture of human m...Background: Daphne Mucronata extract has a decreasing effect on the size of breast adenocarcinoma in rats. So in this study, the effect of Daphne Mucronata purified diterpene were investigated on co culture of human monocytes and two human leukemia cell lines (K562, CCRF-CEM). Materials and Methods: Each cell line mono-layer culture, in log phase growth, was treated with 10 to 160 μL of the extract (1 g/ml leave powder) and purified compound (0.94 nM). For a comparative study, Taxol (5 to 40 μM) was used in the presence and absence of LPS. Human monocytes were isolated by adhesion method. TNF-α in cultured media were measured by sensitive biotin-streptoavidin ELISA method. Results: Fifty percent of growth inhibition was shown by 160 μL (1:100 dilution, 0.5 g of the powdered leaves/ml) of the extract and 0.94 nM of the purified component, and there was more inhibition in K562 cells (P < 0.05). Four fold increases in growth inhibition was shown in co culture of isolated human monocytes and leukemia cell lines. There was a direct relationship between monocytes TNF-α secretion and growth inhibition degree. Conclusion: Daphne Mucronata extract and its purified diterpene through increasing monocytes TNF-α releasing, potentially inhibit Leukemia cell line.展开更多
Objectives: Multi-drug resistance (MDR) to chemotherapy remains a major obstacle to overcome in the successful treatment of patients with cancers. It was recently discovered that Leptomycin B (LMB) reduces the paclita...Objectives: Multi-drug resistance (MDR) to chemotherapy remains a major obstacle to overcome in the successful treatment of patients with cancers. It was recently discovered that Leptomycin B (LMB) reduces the paclitaxel-induced MDR in CCRF-CEM/Taxol cells. However, the mechanism remains unclear. Here we sought to explore the mechanism of LMB to reduce the MDR induced by paclitaxel. Results: LMB has remarkable cytotoxic effects in both sensitive CCRF-CEM and resistant CCRF-CEM/Taxol cell lines. The paclitaxel-induced MDR was reduced by 0.013 μm of LMB. Lower concentration of LMB regulated cell cycle progress, in situ expressions of P-gp, MRP1, and LRP, expression of CRM1, and localization of P-gp and CRM1 in CCRF-CEM/taxol cells. Study Design: Cytotoxicity of LMB on cancerous cell lines was determined by MTT assay. Cell cycle progress and in situ expressions of P-gp, MRP1, and LRP were analyzed by flow cytometry. Expression of CRM1 in the cells was examined by Western blot. And co-localization between P-gp and CRM1 was determined by laser confocal microscopy. Conclusion: The paclitaxel-induced MDR of CCRFCEM/Taxol cells was reduced by lower concentration of LMB. The mechanisms might be related to decreasing in situ expression of drug transporter proteins, promoting cell cycle progress, and altering co-localization between P-gp and CRM1 in the resistant cells.展开更多
文摘Background: Daphne Mucronata extract has a decreasing effect on the size of breast adenocarcinoma in rats. So in this study, the effect of Daphne Mucronata purified diterpene were investigated on co culture of human monocytes and two human leukemia cell lines (K562, CCRF-CEM). Materials and Methods: Each cell line mono-layer culture, in log phase growth, was treated with 10 to 160 μL of the extract (1 g/ml leave powder) and purified compound (0.94 nM). For a comparative study, Taxol (5 to 40 μM) was used in the presence and absence of LPS. Human monocytes were isolated by adhesion method. TNF-α in cultured media were measured by sensitive biotin-streptoavidin ELISA method. Results: Fifty percent of growth inhibition was shown by 160 μL (1:100 dilution, 0.5 g of the powdered leaves/ml) of the extract and 0.94 nM of the purified component, and there was more inhibition in K562 cells (P < 0.05). Four fold increases in growth inhibition was shown in co culture of isolated human monocytes and leukemia cell lines. There was a direct relationship between monocytes TNF-α secretion and growth inhibition degree. Conclusion: Daphne Mucronata extract and its purified diterpene through increasing monocytes TNF-α releasing, potentially inhibit Leukemia cell line.
文摘Objectives: Multi-drug resistance (MDR) to chemotherapy remains a major obstacle to overcome in the successful treatment of patients with cancers. It was recently discovered that Leptomycin B (LMB) reduces the paclitaxel-induced MDR in CCRF-CEM/Taxol cells. However, the mechanism remains unclear. Here we sought to explore the mechanism of LMB to reduce the MDR induced by paclitaxel. Results: LMB has remarkable cytotoxic effects in both sensitive CCRF-CEM and resistant CCRF-CEM/Taxol cell lines. The paclitaxel-induced MDR was reduced by 0.013 μm of LMB. Lower concentration of LMB regulated cell cycle progress, in situ expressions of P-gp, MRP1, and LRP, expression of CRM1, and localization of P-gp and CRM1 in CCRF-CEM/taxol cells. Study Design: Cytotoxicity of LMB on cancerous cell lines was determined by MTT assay. Cell cycle progress and in situ expressions of P-gp, MRP1, and LRP were analyzed by flow cytometry. Expression of CRM1 in the cells was examined by Western blot. And co-localization between P-gp and CRM1 was determined by laser confocal microscopy. Conclusion: The paclitaxel-induced MDR of CCRFCEM/Taxol cells was reduced by lower concentration of LMB. The mechanisms might be related to decreasing in situ expression of drug transporter proteins, promoting cell cycle progress, and altering co-localization between P-gp and CRM1 in the resistant cells.
