Vaticanol C, a novel resveratrol tetramer, reduces lymph node and lung metastases of mouse mammary carcinoma carrying p53 mutation

Purpose The effects of vaticanol C (Vat-C), a novel resveratrol tetramer, were studied in a mouse metastatic mammary cancer model carrying mutations in p53 that produce a metastatic spectrum similar to that seen in human breast cancers. Methods Mammary tumors, induced by inoculation of syngeneic BALB/c mice with BJMC3879 cells, were subsequently treated with Vat-C at 0, 100 and 200 ppm in their diet. Results The in vitro study demonstrated that Vat-C induced apoptosis, as inferred by morphological changes, nucleosomal DNA fragmentation and elevated activities of caspases. Although tumor volumes were not apparently suppressed in mice treated with Vat-C, the multiplicity of lymph node metastasis was significantly decreased in the 200-ppm group. Furthermore, the multiplicity of lung metastasis was also significantly lower in the 200-ppm group. In any category of organ metastasis, the number of organs with metastasis tended to be lower in the 200-ppm group, but these findings were not statistically significant. The levels of apoptosis were significantly higher in the 200-ppm group, but DNA synthesis only a tended to be lower in this group. Microvessel density in tumors also tended to be lower in the Vat-C-treated groups. Moreover, the numbers of lymphatic vessels having intraluminal tumor cells was significantly lower in mammary tumors of mice given 100 and 200-ppm Vat-C, indicating a reduction in migrating tumor cells into the lymphatic vessels of tumor tissue. Conclusions These results suggest that the observed antimetastatic activity of Vat-C may be of clinical significance as an adjuvant therapy in metastatic human breast cancer having p53 mutations, and may also be useful as a chemopreventative of breast cancer development.