Stark Nicole, Gridling Manuela, Madlener Sibylle, Bauer Sabine, Lackner Andreas, Popescu Ruxandra, Diaz Rene, Tut Foster M, Vo Thanh-Phuong Nha, Vonach Caroline, Giessrigl Benedikt, Saiko Philipp, Grusch Michael, Fritzer-Szekeres Monika, Szekeres Thomas, Kopp Brigitte, Frisch Richard, Krupitza Georg
Institute of Clinical Pathology, Medical University of Vienna, Vienna, Austria.
Int J Mol Med. 2009 Oct;24(4):513-21. doi: 10.3892/ijmm_00000260.
The Aracea Anthurium schlechtendalii and Syngonium podophyllum are traditional remedies for the treatment of severe and chronic inflammatory conditions. We cross-examined these plants regarding their anti-neoplastic properties, because several anti-inflammatory molecular targets are common for both pathologic conditions due to similar signalling pathways. Two malignant cell lines, HL-60 and MCF-7, were treated with increasing concentrations of plant extracts of increasing polarity. The potential of the extracts to inhibit the cell cycle and to induce cell death was investigated, because these are relevant endpoints to assess the anti-cancer potential in vitro and the protein expression and cell cycle distribution upon exposure to the strongest extract was analysed. Extracts from S. podophyllum were rather ineffective, but the freeze-dried (but not air-dried) roots of A. schlechtendalii exhibited strong growth inhibitory and apoptosis-inducing properties. In HL-60 cells 50% proliferation inhibition was achieved by 1.7 microg dichloromethane extract/ml medium and correlated with the activation of Chk2, down-regulation of Cdc25A, suppression of cyclin D1 level, and transient induction of p21. This extract efficiently triggered apoptosis, which was confirmed by caspase 3 activation. The polymerisation of alpha-tubulin and its subsequent degradation that depleted the cells from the G2/M contributed to apoptosis induction, because proper spindle-formation during mitosis is mandatory for survival. In conclusion, we demonstrated that A. schlechtendalii root extract specifically targeted carcinogenic mechanisms, because Cdc25A and cyclin D1 are oncogenes that are frequently overexpressed in a variety of cancer entities and further, this extract affected microtubule function reminiscent of taxol.
天南星科的安祖花和合果芋是治疗严重和慢性炎症的传统药物。我们对这些植物的抗肿瘤特性进行了交叉研究，因为由于信号通路相似，几种抗炎分子靶点在这两种病理状况中是共有的。用极性递增的植物提取物的递增浓度处理两种恶性细胞系HL-60和MCF-7。研究了提取物抑制细胞周期和诱导细胞死亡的潜力，因为这些是评估体外抗癌潜力的相关终点，并分析了暴露于最强提取物后的蛋白质表达和细胞周期分布。合果芋的提取物效果不佳，但安祖花的冻干（而非风干）根表现出强大的生长抑制和凋亡诱导特性。在HL-60细胞中，1.7微克二氯甲烷提取物/毫升培养基可实现50%的增殖抑制，这与Chk2的激活、Cdc25A的下调、细胞周期蛋白D1水平的抑制以及p21的短暂诱导相关。该提取物有效触发了凋亡，这通过半胱天冬酶3的激活得到证实。α-微管蛋白的聚合及其随后的降解使细胞从G2/M期耗尽，这有助于凋亡诱导，因为有丝分裂期间正确的纺锤体形成对存活至关重要。总之，我们证明安祖花根提取物特异性靶向致癌机制，因为Cdc2�A和细胞周期蛋白D1是在多种癌症实体中经常过度表达的癌基因，此外，该提取物影响微管功能，类似于紫杉醇。
