Vaticanol C, a novel resveratrol tetramer, reduces lymph node and lung metastases of mouse mammary carcinoma carrying p53 mutation.
OBJECTIVE
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.
Shibata
Masa-Aki
MA
Department of Anatomy and Cell Biology, Division of Basic Medicine I, Osaka Medical College, 2-7, Daigaku-machi, Takatsuki, Japan. shibatam@art.osaka-med.ac.jp
Akao
Yukihiro
Y
Shibata
Eiko
E
Nozawa
Yoshinori
Y
Ito
Tetsuro
T
Mishima
Satoshi
S
Morimoto
Junji
J
Otsuki
Yoshinori
Y
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D017209:Apoptosis; D001835:Body Weight; D005260:Female; D016158:Genes, p53; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D008207:Lymphatic Metastasis / Q000517:prevention & control*; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D013267:Stilbenes / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; C459559:vaticanol C