Inhibition of cancer cell proliferation and apoptosis-inducing activity of fungal taxol and its precursor baccatin III purified from endophytic Fusarium solani.
Inhibition of cancer cell proliferation and apoptosis-inducing activity of fungal taxol and its precursor baccatin III purified from endophytic Fusarium solani.
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DOI：
10.1186/1475-2867-13-105
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发表时间：
2013-10-23
影响因子：
5.8
通讯作者：
Jayabaskaran C
中科院分区：
文献类型：
--
作者：
Chakravarthi BV;Sujay R;Kuriakose GC;Karande AA;Jayabaskaran C
紫杉醇（通用名紫杉醇）是一种植物源性抗肿瘤药物，广泛用于治疗乳腺癌、卵巢癌和肺癌，最初是从太平洋红豆杉（Taxus brevifolia）的树皮中分离出来的。该药物的供应有限，促使人们努力寻找替代来源，例如化学合成、红豆杉属物种的组织和细胞培养，这两种来源都很昂贵且产量低。微生物发酵过程将是降低成本和提高产量的首选方法。之前我们报道过从T. celebica中分离的F. solani在液体培养物中产生紫杉醇及其前体浆果赤霉素III J Biosci 33:259-67, 2008。本研究旨在评估从T. celebica中分离的真菌紫杉醇和真菌浆果赤霉素III对癌细胞系增殖的抑制和诱导细胞凋亡。单独培养HeLa、HepG2、Jurkat、Ovcar3和T47D等细胞系，并根据实验要求用真菌紫杉醇、浆果赤霉素III（加或不加caspase抑制剂）处理。检查了它们对细胞凋亡诱导的功效。真菌紫杉醇和浆果赤霉素 III 均抑制多种癌细胞系的细胞增殖，真菌紫杉醇的 IC50 范围为 0.005 至 0.2 μM，真菌浆果赤霉素 III 的 IC50 范围为 2 至 5 μM。它们还诱导 JR4-Jurkat 细胞凋亡，可能与抗凋亡 Bcl2 和线粒体膜电位损失有关，并且不受 caspase-9、-2 或 -3 抑制剂的影响，但在 caspase-10 抑制剂存在时被阻止。在用真菌紫杉醇和浆果赤霉素 III 处理的细胞中也观察到 DNA 断裂。真菌紫杉醇和浆果赤霉素 III 表现出的细胞毒性活性涉及相同的机制，依赖于 caspase-10 和线粒体膜电位损失，其中紫杉醇具有更大的细胞毒性潜力。
Taxol (generic name paclitaxel), a plant-derived antineoplastic agent, used widely against breast, ovarian and lung cancer, was originally isolated from the bark of the Pacific yew, Taxus brevifolia. The limited supply of the drug has prompted efforts to find alternative sources, such as chemical synthesis, tissue and cell cultures of the Taxus species both of which are expensive and yield low levels. Fermentation processes with microorganisms would be the methods of choice to lower the costs and increase yields. Previously we have reported that F. solani isolated from T. celebica produced taxol and its precursor baccatin III in liquid grown cultures J Biosci 33:259-67, 2008. This study was performed to evaluate the inhibition of proliferation and induction of apoptosis of cancer cell lines by the fungal taxol and fungal baccatin III of F. solani isolated from T. celebica. Cell lines such as HeLa, HepG2, Jurkat, Ovcar3 and T47D were cultured individually and treated with fungal taxol, baccatin III with or without caspase inhibitors according to experimental requirements. Their efficacy on apoptotic induction was examined. Both fungal taxol and baccatin III inhibited cell proliferation of a number of cancer cell lines with IC50 ranging from 0.005 to 0.2 μM for fungal taxol and 2 to 5 μM for fungal baccatin III. They also induced apoptosis in JR4-Jurkat cells with a possible involvement of anti-apoptotic Bcl2 and loss in mitochondrial membrane potential, and was unaffected by inhibitors of caspase-9,-2 or -3 but was prevented in presence of caspase-10 inhibitor. DNA fragmentation was also observed in cells treated with fungal taxol and baccatin III. The cytotoxic activity exhibited by fungal taxol and baccatin III involves the same mechanism, dependent on caspase-10 and membrane potential loss of mitochondria, with taxol having far greater cytotoxic potential.
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影响因子：
4.1
作者：
Gangadevi, V.;Muthumary, J.
通讯作者：
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