Research progress on the source, production, and anti-cancer mechanisms of paclitaxel / 中国天然药物

Paclitaxel, a tetracyclic diterpenoid compounds, was firstly isolated from the bark of the Pacific yew trees. Currently, as a low toxicity, high efficiency, and broad-spectrum natural anti-cancer drug, paclitaxel has been widely used against ovarian cancer, breast cancer, uterine cancer, and other cancers. As the matter of fact, natural paclitaxel from Taxus species has been proved to be environmentally unsustainable and economically unfeasible. For this reason, researchers from all over the world are devoted to searching for new ways of obtaining paclitaxel. At present, other methods, including artificial cultivation of Taxus plants, microbial fermentation, chemical synthesis, tissue and cell culture have been sought and developed subsequently. Meanwhile, the biosynthesis of paclitaxel is also an extremely attractive method. Unlike other anti-cancer drugs, paclitaxel has its unique anti-cancer mechanisms. Here, the source, production, and anti-cancer mechanisms of paclitaxel were summarized and reviewed, which can provide theoretical basis and reference for further research on the production, anti-cancer mechanisms and utilization of paclitaxel.

In Vivo Distribution and Therapeutic Efficacy of Magnetic Liposomes Containing Paclitaxel for Lung Cancer in Nude Mice / 中国药房

OBJECTIVE:To investigate the distribution of magnetic nanoparticle embedding Paclitaxel in vivo and its curative effect on lung cancer in mice model.METHODS:The magnetic lipsomes containing Paclitaxel and the Paclitaxel liposomes were injected into caudal vein of mice,and which were exposed to magnetic field of 0.5T.The concentrations of the two drugs in different organs were determined.The lung cancer model was established in mice and the therapeutic efficacy of the different drugs on tumor was evaluated by comparing the weight of mice before and after administration.RESULTS: In the mice treated with magnetic liposome containing Paclitaxel,the drug concentration in lung which was exposed to magnetic field was significantly higher than that in the others sites,and a steady state concentration was reached quickly in lung after administration,but gradually in other organs.In the mice treated with liposomes containing paclitaxel,a steady state concentration was reached gradually in lung.The tumor control rate was 27.53% in mice treated with magnetic liposome containing Paclitaxel plus magnetic field intervention,significantly higher than in the control group.CONCLUSION: The result shows that magnetic targeting drug delivery is an effective drug delivery system,by which,the drugs can aggregate to the target site in large quantity which may lead to a reduced distribution of drugs in non-target sites.

The anticancer effect of paclitaxel(taxol.) in oral squamous cell carcinoma xenograft

Effects of treatment sequence of cisplatin and paclitaxel (taxol) on cell cycle and cell death in NIHOVCAR-3 cell line / 대한산부인과학회잡지

The overt effects of the anticancer drugs such as cisplatin and taxol appear to be DNA modification and microtubule stabilization respectively. But the mechanism by which these drugs affect tumor cell cycle perturbation and their correlation to apoptosis and cytotoxicity are not well understood, especially in combined sequential treatment of cisplatin and paclitaxel (taxol). In this study, to elucidate the action mechanisms as a function of cell cycle changes and cytotoxicities and to determine the adequate treatment sequence of cisplatin and taxol to acquire more enhanced cytotoxic effects when they are combined, we evaluated the cell cycle perturbations and its correlation to cytotoxic effects, which is measured by the extents of apoptosis and the fractions of cellular debris and live cells after combination treatment of cisplatin and taxol changing their treatment sequences in NIHOVCAR-3 ovarian cancer cell line. Our results were as follows; (1) The accumulation in S phase inhibited the entrance of tumor cells to G2M phase when the cisplatin treatment was preceded to taxol in their combination. (2) The tumor cells were not accumulated in S phase but most of them entered to and accumulated in G2M phase and they were leading to cell death when the taxol treatment was preceded to cisplatin in their combination. (3) Apoptotic peaks in taxol pretreatment group were detected earlier and persisted longer than that of cisplatin pretreatment group. (4) The cytotoxicities represented by the decreased fractions of live cells and the increased fractions of cellular debris were higher in taxol pretreatment group than those of cisplatin pretreatment group. These results suggested that the taxol pretreatment is more effective in combination of cisplatin and taxol and the relative decrease in the cytotoxicity in cisplatin pretreatment group was considered to be derived from the inhibition of entrance of tumor cells to G2M and protected them from the action by taxol. From these results, we concluded that the taxol pretreatment will enhance the cytotoxic effects to tumor cells when cisplatin and taxol will be administered and it indicates that correlations between cell cycle perturbation, apoptosis and cell death have to be considered in the future combination treatment of other drugs and in the development of new treatment regimens.

Protective Effect of PKC Affecting Taxol-induced Cytotoxicity in MCF-7 Cells / 대한해부학회지

Paclitaxel (taxol) is known as effective drug inhibition of cell cycle encouraging activity in human ovarian and metastatic breast cancers and malignant melanoma. It is an antimicrotubule agent that is believed to mediate its antineoplastic effects by inducing mitotic arrest followed by apoptosis. The relation between phorbol 12 myristate 13 acetate (PMA), protein kinase C (PKC) activator, and taxol-induced apoptosis is not well understood until now. This study was performed to investigate the effects of PMA on the signal transduction pathways of taxol-induced apoptosis in MCF-7 human breast carcinoma cells. Taxol-induced apoptosis is attenuated by curcumine, JNK inhibitor, and pyrrolidine dithiocarbamate (PDTC), inhibitor of NFkB. Pretreatment with PKC activator (PMA) or protein kinase A (PKA) activators (forskolin and dibutyryl cAMP) inhibited taxol-induced apoptosis in MCF-7 cells. In addition, thapsigargin, a specific inhibitor of endoplasmic reticulum(ER) Ca(2+)-ATPase and CaCl2, also blocked the activation of caspases by taxol. From these results suggest that taxol-induced apoptosis may be mediated via JNK or NFkB pathway and PKC activation.

Effect of explant source from different maternal tree and medium composition on callus growth and paclitaxel yield of Taxus chinensis var. mairei / 中草药

Objective To establish and optimize the technology and method of producing large quantity and high-paclitaxe yield callus of 〖WTBX〗Taxus chinensis var. mairei. Methods Wild maternal tree grown in Lingchuan County of Shanxi Province and cultivated tree grown in Xi′an were used as explant source. And the optimum maternal tree for explant cutting, optimum explant type, basic medium, composition and concentration of growth regulators in medium and so on, which were factors of affecting on callus induction, growth and paclitaxe yield, were examined in a series order. Results The juvenile stem segments were the optimum explants because of their earlier and higher rate callus induction than that of other explants. Medium Y5: MS+2,4-D 4.0 mg/L+KIN 1.0 mg/L or medium B5 Ⅲ: B5+2,4-D 3.0 mg/L+KIN 0.1 mg/L+Phe 0.1 mol/L was confirmed optimum callus induction medium in which callus induction rate had reached to 100%. In callus subculture medium, lower concentration of 2,4-D (0.5—3 mg/L) always increased callus growth, but higher concentration of 2,4-D (8 mg/L) reduced callus growth. When 2,4-D concentration was suitable, callus grown on B5 medium displayed lighter browning and faster tissue growth than that on MS medium. Further more, HPLC analysis confirmed that the paclitaxel yield in callus grown on medium MSⅢ was highest and had reached 0.004% of callus dry weight. In a general condition, the level of paclitaxel in calli derived from juvenile stems of wild maternal tree was higher than that in calli initiated from cultivated maternal tree's juvenile stems. Conclusion The optimization sequence of obtaining a large quantity and high-paclitaxe yield callus of T. chinensis var. mairei are dividing juvenile stem segments from wild maternal tree in May and culturing on medium Y5 or B5 Ⅲ for callus induction. After the calli having been subcultured on the same medium for 8—10 generations, one or two generations are recultured on medium MSⅢ. Finally, the calli with more paclitaxel are obtained by extracting paclitaxel out of it.