beta-Carboline alkaloids are natural products widely distributed in plants and also found in alcoholic beverages, well-cooked foods and tobacco smoke. Various authors have reported genotoxic activities of several carboline in prokaryotic and eukaryotic cells that have been attributed to their abilities to intercalate into DNA. But studies on the genotoxic and on the cytotoxic potencies in human cells in vitro are not found in the literature. In the present study the toxicities of one full aromatic beta-carboline alkaloid (harmine) and one dihydro-beta-carboline alkaloid (harmaline) were evaluated by means of two in vitro human cell assays: the cytochalasin-B blocked micronucleus (CBMN) assay and the viability/colony formation assay with four different human cultured non-transformed (CCD18Lu) and transformed (HeLa, C33A and SW480) cells. Neither alkaloid was able to induce micronuclei levels above that of control levels in a wide range of doses tested; although, harmine at the highest concentrations assayed induced apoptotic as well as necrotic cells. Harmine produced a good viability of all cell lines assayed (control and tumor) while harmaline significantly reduced the viability of transformed and non-transformed cell lines in a dose-dependent manner. Harmine displayed a dose-dependent inhibitory effect on cell proliferation against all human carcinoma cells, but the SW480 transformed cell line showed a higher sensitivity. These results suggested that harmine was identified as a useful inhibitor of tumor development.

译文

β-Carboline生物碱是天然产物,广泛分布于植物中,也存在于酒精饮料,煮熟的食物和烟草烟雾中。各种作者报道了原核和真核细胞中几种carboline的遗传毒性活性,这归因于它们插入DNA的能力。但是在文献中未发现有关体外人类细胞的遗传毒性和细胞毒性能力的研究。在本研究中,通过两种体外人类细胞测定法评估了一种全芳香族 β-碳环碱生物碱 (harmine) 和一种二氢-β-碳环碱生物碱 (harmaline) 的毒性: 细胞松弛素-B用四种不同的人类培养的未转化 (CCD18Lu) 和转化 (HeLa,C33A和SW480) 细胞阻断微核 (CBMN) 测定和活力/集落形成测定。在广泛的测试剂量范围内,这两种生物碱都无法诱导高于对照水平的微核水平; 尽管,在最高浓度下测定的harmine诱导了凋亡和坏死细胞。Harmine产生了所有测定的细胞系 (对照和肿瘤) 的良好活力,而harmaline以剂量依赖性方式显着降低了转化和非转化细胞系的活力。Harmine对所有人类癌细胞的细胞增殖均表现出剂量依赖性抑制作用,但SW480转化的细胞系显示出更高的敏感性。这些结果表明,harmine被确定为肿瘤发展的有用抑制剂。

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