Synthetic α‐mangostin dilaurate strongly suppresses wide‐spectrum organ metastasis in a mouse model of mammary cancer

摘要

We previously reported that, in a mouse model of mammary cancer, α‐mangostin alone exhibits anti‐metastatic properties. To enhance this anti‐metastatic effect, we examined the efficacy of synthetic α‐mangostin dilaurate (MGD), prepared by adding lauric acid to α‐mangostin, in the same experimental system wherein mice bearing mammary tumors are exposed to dietary MGD at 0, 2000 and 4000 ppm. Lauric acid has a high propensity for lymphatic absorption, which is the most common pathway of initial dissemination of many solid malignancies. Both mammary tumor volumes and wide‐spectrum organ metastasis were markedly reduced at 2000 and 4000 ppm: furthermore, survival in the 4000‐ppm group was significantly greater than in control mice. Apoptosis in mammary carcinomas was also significantly increased in the 4000‐ppm group, whereas blood microvessel density and lymphatic vessel invasion were markedly reduced. In real‐time PCR analyses of tumor samples, increased p21 and decreased Pcna expression were observed with 4000 ppm but values were not statistically significant when compared to expression in control tumors. However, exposure to 4000 ppm significantly decreased expression of phospho‐Akt (Ser473/Thr308) as compared to the control, indicating a role in the anti‐tumorigenic effects of MGD. These findings suggest that MGD may be useful for adjuvant therapy and chemoprevention and that conjugated medium‐chain fatty acids may enhance the efficacy of certain chemotherapeutic agents.