Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, China.
BMC Complement Altern Med. 2011 Dec 2;11:123. doi: 10.1186/1472-6882-11-123.
Botanical medicines are increasingly combined with chemotherapeutics as anticancer drug cocktails. This study aimed to assess the chemotherapeutic potential of an extract of Taxus cuspidata (TC) needles and twigs produced by artificial cuttage and its co-effects as a cocktail with 5-fluorouracil (5-FU).
Components of TC extract were identified by HPLC fingerprinting. Cytotoxicity analysis was performed by MTT assay or ATP assay. Apoptosis studies were analyzed by H & E, PI, TUNEL staining, as well as Annexin V/PI assay. Cell cycle analysis was performed by flow cytometry. 5-FU concentrations in rat plasma were determined by HPLC and the pharmacokinetic parameters were estimated using 3p87 software. Synergistic efficacy was subjected to median effect analysis with the mutually nonexclusive model using Calcusyn1 software. The significance of differences between values was estimated by using a one-way ANOVA.
TC extract reached inhibition rates of 70-90% in different human cancer cell lines (HL-60, BGC-823, KB, Bel-7402, and HeLa) but only 5-7% in normal mouse T/B lymphocytes, demonstrating the broad-spectrum anticancer activity and low toxicity to normal cells of TC extract in vitro. TC extract inhibited cancer cell growth by inducing apoptosis and G(2)/M cell cycle arrest. Most interestingly, TC extract and 5-FU, combined as a cocktail, synergistically inhibited the growth of cancer cells in vitro, with Combination Index values (CI) ranging from 0.90 to 0.26 at different effect levels from IC50 to IC90 in MCF-7 cells, CI ranging from 0.93 to 0.13 for IC40 to IC90 in PC-3M-1E8 cells, and CI < 1 in A549 cells. In addition, the cocktail had lower cytotoxicity in normal human cell (HEL) than 5-FU used alone. Furthermore, TC extract did not affect the pharmacokinetics of 5-FU in rats.
The combinational use of the TC extract with 5-FU displays strong cytotoxic synergy in cancer cells and low cytotoxicity in normal cells. These findings suggest that this cocktail may have a potential role in cancer treatment.
植物药作为抗癌药物鸡尾酒，与化疗药物联合应用日益增多。本研究旨在评估人工扦插的紫杉（TC）针和小枝提取物的化疗潜力及其与 5-氟尿嘧啶（5-FU）联合应用的协同作用。
采用高效液相色谱指纹图谱鉴定 TC 提取物的成分。通过 MTT 或 ATP 测定法进行细胞毒性分析。通过 H&E、PI、TUNEL 染色以及 Annexin V/PI 检测分析细胞凋亡。通过流式细胞术进行细胞周期分析。采用 HPLC 测定大鼠血浆中 5-FU 浓度，使用 3p87 软件估算药代动力学参数。采用 Calcusyn1 软件中的互不相容模型进行中值效应分析，以评估协同作用。采用单因素方差分析估计值间差异的显著性。
TC 提取物在不同人癌细胞系（HL-60、BGC-823、KB、Bel-7402 和 HeLa）中达到 70%-90%的抑制率，但在正常小鼠 T/B 淋巴细胞中仅为 5%-7%，表明 TC 提取物在体外具有广谱抗癌活性和对正常细胞的低毒性。TC 提取物通过诱导细胞凋亡和 G2/M 细胞周期阻滞抑制癌细胞生长。最有趣的是，TC 提取物与 5-FU 联合作为鸡尾酒，在体外协同抑制癌细胞生长，在 MCF-7 细胞中，从 IC50 到 IC90 的不同效应水平下，组合指数（CI）值范围为 0.90 至 0.26，在 PC-3M-1E8 细胞中，从 IC40 到 IC90 的 CI 值范围为 0.93 至 0.13，在 A549 细胞中，CI 值小于 1。此外，与单独使用 5-FU 相比，鸡尾酒在正常人类细胞（HEL）中的细胞毒性较低。此外，TC 提取物不影响大鼠体内 5-FU 的药代动力学。
TC 提取物与 5-FU 联合应用在癌细胞中具有较强的细胞毒性协同作用，在正常细胞中细胞毒性较低。这些发现表明，这种鸡尾酒可能在癌症治疗中具有潜在作用。
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