Lim K, Han C, Xu L, et al. Omega-3 polyunsaturated fatty acids inhibit hepatocellular carcinoma cell growth through downregulation of beta-catenin/wnt signaling pathway. Abstract no. 2679. 97th AACR Annual Meeting. Washington, DC.

Omega-3 polyunsaturated fatty acids (w3-PUFAs) are known to suppress the growth of several cancer cells, although the molecular mechanisms for their anticancer actions remain to be further understood.

This study was designed to investigate the effect and mechanism of w3-PUFAs in human hepatocellular carcinoma (HCC) cells.

Treatment of human HCC cells (Hep3B, Huh-7, HepG2) with two w3-PUFAs, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), for 12-48 hours resulted in a dose-dependent inhibition of cell growth, whereas arachidonic acid (AA), a w6-PUFA, exhibited no significant effect. This action likely involves apoptosis, given that DHA treatment induced cleavage form of PARP in Hep3B cells.

Furthermore, DHA and EPA treatment transiently decreased the level of phospho-GSK3-beta protein (but not phospho-AKT) and progressively reduced the beta-catenin protein in Hep3B cells.

Accordingly, DHA treatment also decreased the beta-catenin-mediated TCF-LEF reporter activity and inhibited the expression of c-Met, a beta-catenin-controlled downstream gene.

GSK3-beta inhibitors, LiCl and SB216763, partially prevented DHA-induced reduction of beta-catenin protein and TCF-LEF reporter activity and restored cell growth.

These findings suggest that w3-PUFAs inhibit HCC cell growth partly through down-regulation of phospho-GSK3-beta/beta-catenin/TCF-LEF signaling pathway.

Consequently, administration of w3-PUFA may represent a potential effective therapy for the chemoprevention and treatment of human HCC (This work was supported by NIH grants RO1 CA102325 and RO1 CA106280).

Lim K, Han C, Xu L, et al. Evidence for inhibition of beta-catenin/Wnt signaling in omega-3 polyunsaturated fatty acid-induced apoptosis of human cholangiocarcinoma cells. Abstract no. 2680. 97th AACR Annual Meeting. Washington, DC.

Cholangiocarcinoma is the second most common primary hepatobiliary malignancy in adult.

It has a high mortality rate and currently there is no effective treatment. Given its limited patient survival, a new molecular target is needed for effective chemoprevention and treatment.

Omega-3 polyunsaturated fatty acids (w3-PUFAs) are known to suppress the growth of several cancer cells, although the molecular mechanisms for their anticancer actions are not fully understood.

This study was designed to investigate the potential effect of w3-PUFAs and their mechanism of actions in human cholangiocarcinoma cells.

Treatment of human cholangiocarcinoma cells (CCLP1, HuCCT1, SG231) with two w3-PUFAs, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), for 12-48 hours resulted in a dose-dependent inhibition of cell growth; in contrast, arachidonic acid (AA), a w6-PUFA, had no significant effect.

The observation that DHA induced cleavage form of PARP in CCLP1 cells indicates induction of apoptosis. Furthermore, DHA and EPA treatment transiently decreased the level of phospho-GSK3-beta (but not phospho-AKT) and progressively reduced the level of beta-catenin protein in CCLP1 cells.

DHA treatment also decreased the beta-catenin-mediated TCF-LEF reporter activity and inhibited the expression of c-Met, a bet-catenin-controlled downstream gene. GSK3-beta inhibitors, LiCl and SB216763, partially prevented DHA-induced reduction of beta-catenin protein and TCF-LEF reporter activity, and restored cell growth.

These findings suggest that w3-PUFAs inhibit cholangiocarcinoma cell growth in part through downregulation of phospho-GSK3-beta/beta-catenin/TCF-LEF signaling pathway.

Therefore, utilization of w3-PUFAs may represent a potential effective therapy for the chemoprevention and treatment of human cholangiocarcinoma (This work was supported by NIH grants RO1 CA102325 and RO1 CA106280).