University of Medicine and Pharmacy of Ho Chi Minh City, 41 Dinh Tien Hoang street, District 1, Ho Chi Minh City, Vietnam.
J Ethnopharmacol. 2013 Aug 26;149(1):75-83. doi: 10.1016/j.jep.2013.06.002. Epub 2013 Jun 12.
Crinum latifolium L. (CL) leaf extracts have been traditionally used in Vietnam and are now used all over the world for the treatment of prostate cancer. However, the precise cellular mechanisms of the action of CL extracts remain unclear.
To examine the effects of CL samples on the anti-tumour activity of peritoneal murine macrophages.
The properties of three extracts (aqueous, flavonoid, alkaloid), one fraction (alkaloid), and one pure compound (6-hydroxycrinamidine) obtained from CL, were studied (i) for redox capacities (DPPH and bleaching beta-carotene assays), (ii) on murine peritoneal macrophages (MTT assay) and on lymphoma EL4-luc2 cells (luciferine assay) for cytotoxicity, (iii) on macrophage polarization (production of ROS and gene expression by PCR), and (iv) on the tumoricidal functions of murine peritoneal macrophages (lymphoma cytotoxicity by co-culture with syngeneic macrophages).
The total flavonoid extract with a high antioxidant activity (IC50=107.36 mg/L, DPPH assay) showed an inhibitory action on cancer cells. Alkaloid extracts inhibited the proliferation of lymphoma cells either by directly acting on tumour cells or by activating of the tumoricidal functions of syngeneic macrophages. The aqueous extract induced mRNA expression of tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin 6 (IL-6) indicating differentiation of macrophages into pro-inflammatory M1 polarized macrophages. The total flavonoid, alkaloid extracts and an alkaloid fraction induced the expression of the formyl peptide receptor (FPR) on the surface of the polarized macrophages that could lead to the activation of macrophages towards the M1 phenotype. Aqueous and flavonoid extracts enhanced NADPH quinine oxido-reductase 1 (NQO1) mRNA expression in polarized macrophages which could play an important role in cancer chemoprevention. All the samples studied were non-toxic to normal living cells and the pure alkaloid tested, 6-hydroxycrinamidine, was not active in any of the models investigated.
Our results indicate that CL extracts and alkaloid fraction (but not pure 6-hydroxycrinamidine) inhibit the proliferation of lymphoma cells in multiple pathways. Our results are in accordance with traditional usage and encourage further studies and in vivo assays.
长叶文殊兰（CL）叶提取物在越南传统上被用于治疗前列腺癌，现已在全球范围内使用。然而，CL 提取物作用的确切细胞机制仍不清楚。
研究 CL 样本对腹腔鼠巨噬细胞抗肿瘤活性的影响。
研究了从 CL 中获得的三种提取物（水提物、类黄酮、生物碱）、一个馏分（生物碱）和一种纯化合物（6-羟基文殊兰碱）的特性（i）还原能力（DPPH 和胡萝卜素漂白测定），（ii）对腹腔鼠巨噬细胞（MTT 测定）和淋巴瘤 EL4-luc2 细胞（萤光素酶测定）的细胞毒性，（iii）对巨噬细胞极化（ROS 产生和 PCR 基因表达）的影响，以及（iv）对腹腔鼠巨噬细胞的杀肿瘤功能（与同种巨噬细胞共培养的淋巴瘤细胞毒性）。
具有高抗氧化活性（IC50=107.36mg/L，DPPH 测定）的总类黄酮提取物对癌细胞表现出抑制作用。生物碱提取物通过直接作用于肿瘤细胞或激活同种巨噬细胞的杀肿瘤功能来抑制淋巴瘤细胞的增殖。水提物诱导肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素 6（IL-6）的 mRNA 表达，表明巨噬细胞向促炎 M1 极化巨噬细胞分化。总类黄酮、生物碱提取物和生物碱馏分诱导极化巨噬细胞表面的甲酰肽受体（FPR）表达，这可能导致巨噬细胞向 M1 表型激活。水提物和类黄酮提取物增强了极化巨噬细胞中烟酰胺腺嘌呤二核苷酸磷酸醌氧化还原酶 1（NQO1）的 mRNA 表达，这在癌症化学预防中可能发挥重要作用。研究中所有的样本对正常活细胞均无毒性，所测试的纯生物碱 6-羟基文殊兰碱在所有研究模型中均无活性。
我们的结果表明，CL 提取物和生物碱馏分（而非纯 6-羟基文殊兰碱）通过多种途径抑制淋巴瘤细胞的增殖。我们的结果与传统用途一致，并鼓励进一步的研究和体内试验。
