Marlene and Stewart Greenebaum Cancer Center, Baltimore, Maryland 21201, USA.
Anticancer Drugs. 2012 Feb;23(2):200-11. doi: 10.1097/CAD.0b013e32834b85e8.
Breast cancer mortality is primarily due to the occurrence of metastatic disease. We have identified a novel potential therapeutic agent derived from an edible root of the plant Colocasia esculenta, commonly known as taro, which has demonstrable activity in a preclinical model of metastatic breast cancer and that should have minimal toxicity. We have shown for the first time that a water-soluble extract of taro (TE) potently inhibits lung-colonizing ability and spontaneous metastasis from mammary gland-implanted tumors, in a murine model of highly metastatic estrogen receptor, progesterone receptor and Her-2/neu-negative breast cancer. TE modestly inhibits the proliferation of some, but not all, breast and prostate cancer cell lines. Morphological changes including cell rounding were observed. Tumor cell migration was completely blocked by TE. TE treatment also inhibited prostaglandin E2 (PGE2) synthesis and downregulated cyclooxygenase 1 and 2 mRNA expression. We purified the active compound(s) to near homogeneity with antimetastatic activity comparable with stock TE. The active compound with a native size of approximately 25 kDa contains two fragments of nearly equal size. The N-terminal amino acid sequencing of both fragments reveals that the active compound is highly related to three taro proteins: 12-kDa storage protein, tarin and taro lectin. All are similar in terms of amino acid sequence, posttranslational processing and all contain a carbohydrate-binding domain. This is the first report describing compound(s) derived from taro that potently and specifically inhibits tumor metastasis.
乳腺癌的死亡率主要归因于转移性疾病的发生。我们从一种名为芋头的植物的可食用根部中鉴定出一种新型潜在治疗药物,芋头在转移性乳腺癌的临床前模型中具有明显的活性,且应该具有最小的毒性。我们首次表明,芋头的水溶性提取物(TE)能够强烈抑制高度转移性雌激素受体、孕激素受体和 Her-2/neu 阴性乳腺癌小鼠模型中的肺定植能力和自发转移。TE 适度抑制一些,但不是全部,乳腺癌和前列腺癌细胞系的增殖。观察到包括细胞圆化在内的形态变化。TE 完全阻断肿瘤细胞迁移。TE 处理还抑制前列腺素 E2(PGE2)合成并下调环氧化酶 1 和 2 mRNA 表达。我们将具有抗肿瘤转移活性的活性化合物纯化至近乎均一,其活性与原始 TE 相当。具有约 25 kDa 天然大小的活性化合物包含两个几乎相等大小的片段。两个片段的 N 末端氨基酸测序表明,活性化合物与三种芋头蛋白高度相关:12 kDa 储存蛋白、芋蛋白和芋头凝集素。它们在氨基酸序列、翻译后加工方面均相似,且均含有碳水化合物结合结构域。这是首次描述芋头衍生的化合物能够强烈且特异性地抑制肿瘤转移的报告。