Abstract
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.