Shrestha Gajendra, El-Naggar Atif M, St Clair Larry L, O'Neill Kim L
Department of Biology, Brigham Young University, Provo, UT, USA; M. L. Bean Life Science Museum, Brigham Young University, Provo, UT, USA.
Phytother Res. 2015 Jan;29(1):100-7. doi: 10.1002/ptr.5233. Epub 2014 Sep 24.
Cancer is the second leading cause of human deaths in the USA. Despite continuous efforts to treat cancer over the past 50 years, human mortality rates have not decreased significantly. Natural products, such as lichens, have been good sources of anticancer drugs. This study reports the cytotoxic activity of crude extracts of 17 lichen species against Burkitt's lymphoma (Raji) cells. Out of the 17 lichen species, extracts from 14 species showed cytotoxicity against Raji cells. On the basis of IC50 values, we selected Xanthoparmelia chlorochroa and Tuckermannopsis ciliaris to study the mechanism of cell death. Viability of normal lymphocytes was not affected by the extracts of X. chlorochroa and T. ciliaris. We found that extracts from both lichens decreased proliferation, accumulated cells at the G0 /G1 stage, and caused apoptosis in a dose-dependent manner. Both lichen extracts also caused upregulation of p53. The T. ciliaris extract upregulated the expression of TK1 but X. chlorochroa did not. We also found that usnic, salazinic, constictic, and norstictic acids were present in the extract of X. chlorochroa, whereas protolichesterinic acid in T. ciliaris extracts. Our data demonstrate that lichen extracts merit further research as a potential source of anticancer drugs.
癌症是美国人类死亡的第二大主要原因。尽管在过去50年里一直在不断努力治疗癌症,但人类死亡率并未显著下降。天然产物,如地衣,一直是抗癌药物的良好来源。本研究报告了17种地衣物种的粗提物对伯基特淋巴瘤(Raji)细胞的细胞毒性活性。在这17种地衣物种中,14种的提取物对Raji细胞显示出细胞毒性。基于半数抑制浓度(IC50)值,我们选择了黄绿黄髓衣和睫状塔克衣来研究细胞死亡机制。正常淋巴细胞的活力不受黄绿黄髓衣和睫状塔克衣提取物的影响。我们发现,两种地衣的提取物均以剂量依赖的方式降低细胞增殖、使细胞在G0/G1期积累并导致细胞凋亡。两种地衣提取物还导致p53上调。睫状塔克衣提取物上调胸苷激酶1(TK1)的表达,但黄绿黄髓衣提取物则没有。我们还发现,黄绿黄髓衣提取物中存在松萝酸、沙拉子酸、扁枝衣酸和降斑点酸,而睫状塔克衣提取物中存在原地衣硬脂酸。我们的数据表明,地衣提取物作为潜在的抗癌药物来源值得进一步研究。