Taxane recovery from cells of Taxus in micro- and hypergravity
Taxane recovery from cells of Taxus in micro- and hypergravity
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DOI：
10.1016/s0094-5765(98)00138-6
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发表时间：
1998-01-01
影响因子：
3.5
通讯作者：
Havel, L
中科院分区：
文献类型：
--
作者：
Durzan, DJ;Ventimiglia, F;Havel, L
东北红豆杉细胞悬浮培养产生紫杉烷，紫杉烷以游离态和结合态生物碱的形式从细胞外表面释放到培养基中。紫杉醇(Taxol(TM))是一种供不应求的抗癌药物。它具有来源于巴卡菌素III的紫杉烷环和C-13苯基异丝氨酸侧链。这种药物是在大范围的重力作用下产生的。紫杉醇、巴卡菌素III和C-13苯异丝氨酸侧链的单抗和多克隆抗体被结合在多重标记研究中，以定位紫杉烷和紫杉醇在细胞表面或释放到培养基中的颗粒上。生物反应器容器的设计改变了在模拟微重力下从细胞中回收的紫杉烷的组成。在10(-2)和2.10(-4)g剂量下，紫杉烷回收率降低，但生物量增长和紫杉醇百分比显著增加。当紫杉醇含量为1~24.g时，紫杉醇总量显著恢复，紫杉醇百分含量较低。结合的紫杉醇也定位于个别凋亡细胞的富含核酸内切酶的碎裂核中。提出了一个由TCH(触摸)基因组成的模型，该基因编码的酶可以修饰细胞壁中含有紫杉烷的木聚糖残基，细胞质对重力的钙感应，以及细胞核对凋亡的易感性。这将药物生产基因组的适应性生理和生化反应与重力结合在一起。(C)1998爱思唯尔科学有限公司。保留所有权利。
Cell suspension cultures of Taxus cuspidata produce taxanes that are released from the outer surface of cells into the culture medium as free and bound alkaloids. Paclitaxel (Taxol(TM)), is an anti-cancer drug in short supply. It has a taxane ring derived from baccatin III and a C-13 phenylisoserine side-chain. This drug is produced over a wide range of gravitational forces. Monoclonal and polyclonal antibodies to paclitaxel, baccatin III, and the C-13 phenylisoserine side chain were combined in multiple-labeling studies to localize taxanes and paclitaxel on cell surfaces or on particles released into the culture medium. Bioreactor vessel design altered the composition of taxanes recovered from cells in simulated microgravity. At 10(-2) and 2.10(-4).g, taxane recovery was reduced but biomass growth and percent paclitaxel was significantly increased. At 1 to 24.g, growth was reduced with a significant recovery of total taxanes with low percent paclitaxel. Bound paclitaxel was also localized in endonuclease-rich fragmenting nuclei of individual apoptotic cells. A model is presented comprising TCH (touch) genes encoding enzymes that modify taxane-bearing xylan residues in cell walls, the calcium-sensing of gravitational forces by the cytoplasm, and the predisposition of nuclei to apoptosis. This integrates the adaptive physiological and biochemical responses of drug-producing genomes with gravitational forces. (C) 1998 Elsevier Science Ltd. All rights reserved.