Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Transl Res. 2010 Jun;155(6):305-14. doi: 10.1016/j.trsl.2010.03.002. Epub 2010 Apr 13.
Toona sinensis (TS), which is also known as Cedrela sinensis, belongs to Meliaceae family, the compounds identified from this TS leaves possess a wide range of biologic functions, such as hypoglycemic effects, anti-LDL glycative activity, antioxidant activities, and inhibition of sudden acute respiratory syndrome (SARS) coronavirus replication. However, their effect against cancer cells is not well explored. In this study, to understand the cytotoxic effect and molecular mechanism stimulated by TSL-1 (TS leaf extract fraction) we employed three different non-small-cell lung cancer (NSCLC) cell lines: H441 cells (lung adenocarcinoma), H661 cells (lung large cell carcinoma) and H520 cells (lung squamous cell carcinoma). IC50 value was varied between these three cell lines, the least IC(50) value was observed in TSL-1-treated H661cells. Exposure of NSCLC cells to TSL-1 caused cell-cycle arrest in subG1 phase and caused apoptosis. Moreover, TSL-1 treatment decreased the cell-cycle regulators; cyclin D1 and CDK4 proteins by up regulating p27 expression in a dose-dependent manner. Thus, the TSL-1-induced apoptosis was further confirmed by cell morphology, subG1 peak accumulation, poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) cleavage, propidium iodide (PI)-Annexin-V double staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. The decreased Bcl2 protein level was concurrent with an increased Bax protein level in all 3 cell lines. Additionally, the tumoricidal effect of TSL-1 was measured using a xenograft model, after 5 weeks of TSL-1 treatment by various regimen caused regression of tumor. Taken together both these in vitro and in vivo studies revealed that TSL-1 is a potent inhibitor against NSCLC growth and our provoking result suggest that TSL-1 can be a better nutriceutical as a singlet or along with doublet agents (taxane, vinorelbine, and gemcitabine) for treating NSCLC.
香椿（TS），又名楝科植物，从这种 TS 叶中分离得到的化合物具有广泛的生物学功能，如降血糖作用、抗 LDL 糖化活性、抗氧化活性和抑制严重急性呼吸系统综合症（SARS）冠状病毒复制。然而，它们对癌细胞的作用尚未得到很好的探索。在这项研究中，为了了解 TSL-1（TS 叶提取物级分）刺激的细胞毒性作用和分子机制，我们采用了三种不同的非小细胞肺癌（NSCLC）细胞系：H441 细胞（肺腺癌）、H661 细胞（肺大细胞癌）和 H520 细胞（肺鳞状细胞癌）。这三种细胞系的 IC50 值不同，TSL-1 处理的 H661 细胞的 IC50 值最低。NSCLC 细胞暴露于 TSL-1 会导致细胞周期停滞在 subG1 期并引起细胞凋亡。此外，TSL-1 处理以剂量依赖性方式下调细胞周期调节剂；cyclin D1 和 CDK4 蛋白，同时上调 p27 表达。因此，TSL-1 诱导的细胞凋亡进一步通过细胞形态、subG1 峰积累、多聚（腺苷二磷酸[ADP]-核糖）聚合酶（PARP）裂解、碘化丙啶（PI）-Annexin-V 双重染色和末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）试验得到证实。在所有 3 种细胞系中，Bcl2 蛋白水平降低与 Bax 蛋白水平升高同时发生。此外，TSL-1 的抗肿瘤作用通过异种移植模型进行了测量，在 5 周的 TSL-1 治疗后，通过各种方案引起肿瘤消退。总之，这些体外和体内研究表明，TSL-1 是一种有效的 NSCLC 生长抑制剂，我们的研究结果表明，TSL-1 可以作为一种单一或与二联药物（紫杉烷、长春瑞滨和吉西他滨）联合使用的更好的营养药物来治疗 NSCLC。
