Down-regulating Effect of a Standardized Extract of Cultured Lentinula edodes mycelia on Cortactin in Prostate Cancer Cells Is Dependent on Malignant Potential.

BACKGROUND/AIM: The incidence and mortality rates of prostate cancer have been increasing worldwide. Although prostate cancer cells grow slowly in the local original site, once the cancer cells spread to distant organs they grow rapidly and show very aggressive features. Cortactin is a protein that regulates the actin cytoskeleton and plays crucial roles in cancer metastasis. Up-regulated cortactin is correlated with the metastatic capacity of prostate cancer cells. AHCC®, a standardized extract of cultured Lentinula edodes mycelia, has been previously reported to have cortactin-down-regulating effects on human pancreatic cancer cells. In the present study, the effects of AHCC® treatment on cortactin levels in prostate cancer cells was evaluated. MATERIALS AND METHODS: LNCaP.FGC, DU145, and PC-3 are human prostate cancer cell lines. LNCaP.FGC is well differentiated, androgen-dependent, and poorly metastatic. DU145 is less differentiated, androgen-independent, and moderate metastatic. PC-3 is less differentiated, androgen-independent, and highly metastatic. The effects of AHCC® treatment on cortactin levels in prostate cancer cells was evaluated by western blot. RESULTS: In vitro AHCC® treatment decreased cortactin levels in LNCaP.FGC and DU145 cells but did not change those in PC-3 cells. CONCLUSION: AHCC® treatment down-regulated cortactin expression in poor and moderate metastatic LNCaP.FGC and DU145 cells but showed no effect on cortactin expression in the highly metastatic PC-3 cells. Further studies are required to elucidate the mechanism of the resistance to AHCC® treatment in highly metastatic PC-3 cells.

A Biscuit Containing Fucoxanthin Prevents Colorectal Carcinogenesis in Mice.

Fucoxanthin (Fx) is a critical pigment required for photosynthesis in brown algae and microalgae. Fx is also a dietary marine carotenoid that with potent anticancer activity in vitro and in vivo. Some popular light meals for increased satiety, such as biscuits, cereals, and crackers, are frequently fortified with micronutrients for human health benefits. However, data on the anticancer potential of Fx-supplemented light meals in humans and animal models remain limited. In the present study, we investigated the anticancer effects of a Fx-supplemented biscuit using a carcinogenic murine azoxymethane/dextran sodium sulfate (AOM/DSS) model. We observed that periodic administration of biscuits containing 0.3% Fx (Fx-biscuit) at an interval of 3 days (each 15 h) per week for 15 weeks significantly inhibited colorectal carcinogenesis in AOM/DSS mice. Comprehensive gene analysis demonstrated that the Fx-biscuit significantly altered the expression of 138 genes in the colorectal mucosal tissue of the mice. In particular, the expression of heat shock protein 70 (HSP70) genes, Hspa1b (-35.7-fold) and Hspa1a (-34.9-fold), was markedly downregulated. HSP70 is a polyfunctional chaperone protein that is involved in cancer development. Compared to the control-biscuit group, the number of cells with markedly high fluorescence for HSP70 protein (HSP70high) in colorectal mucosal crypts and adenocarcinomas significantly reduced by 0.3- and 0.2-fold, respectively, in the Fx-biscuit group. Our results suggested that Fx-biscuit possesses chemopreventive potential in the colorectal cancer of AOM/DSS mice via the downregulation of HSP70.