Inhibition of fatty acid synthesis arrests colorectal neoplasm growth and metastasis: Anti-cancer therapeutical effects of natural cyclopeptide RA-XII.

Emerging evidence has shown that metabolism, in particular the synthesis of fatty acids, has great significance for growth and metastasis of colorectal neoplasm. The previous results showed that RA-XII, a natural cyclopeptide isolated from Rubia yunnanensis, inhibits tumor growth and metastasis by AMPK/mTOR/P70S6K pathway and PI3K/AKT/NF-κB pathway. But if or not lipid metabolism involves the antitumor mechanism of RA-XII is not clear. Herein the results indicated that RA-XII reduced the cell motility by decreasing the expressions of β-catenin and β-catenin dependent proteins CD44 and MMP7 in HCT116 cells. Then RA-XII effectively reduced fatty acids levels by decreasing the expression of SREBP-1 and inhibiting the expressions of de novo fatty acid synthesis proteins FASN and SCD. Moreover the decreased cell motility caused by RA-XII was attenuated with the SREBP-1 knockdown. In addition, the in vivo experiments also demonstrated that RA-XII inhibited tumor growth and metastasis via restraining lipogenesis in colorectal neoplasm mouse models. Taken together, these results indicated that RA-XII suppressed the colorectal neoplasm growth and metastasis by inhibition of lipogenesis depended on SREBP-1 suppression.