| First Author | Kubokura N | Year | 2015 |
| Journal | J Pharmacol Sci | Volume | 127 |
| Issue | 4 | Pages | 446-55 |
| PubMed ID | 25913757 | Mgi Jnum | J:302637 |
| Mgi Id | MGI:6509369 | Doi | 10.1016/j.jphs.2015.03.005 |
| Citation | Kubokura N, et al. (2015) Differentiation-inducing factor-3 inhibits intestinal tumor growth in vitro and in vivo. J Pharmacol Sci 127(4):446-55 |
| abstractText | Differentiation-inducing factor-1 (DIF-1) produced by Dictyostelium discoideum strongly inhibits the proliferation of various types of cancer cells by suppression of the Wnt/beta-catenin signal transduction pathway. In the present study, we examined the effect of differentiation-inducing factor-3 (DIF-3), a monochlorinated metabolite of DIF-1 that is also produced by D. discoideum, on human colon cancer cell lines HCT-116 and DLD-1. DIF-3 strongly inhibited cell proliferation by arresting the cell cycle at the G0/G1 phase. DIF-3 reduced the expression levels of cyclin D1 and c-Myc by facilitating their degradation via activation of GSK-3beta in a time and dose-dependent manner. In addition, DIF-3 suppressed the expression of T-cell factor 7-like 2, a key transcription factor in the Wnt/beta-catenin signaling pathway, thereby reducing the mRNA levels of cyclin D1 and c-Myc. Subsequently, we examined the in vivo effects of DIF-3 in Mutyh(-/-) mice with oxidative stress-induced intestinal cancers. Repeated oral administration of DIF-3 markedly reduced the number and size of cancers at a level comparable to that of DIF-1. These data suggest that DIF-3 inhibits intestinal cancer cell proliferation in vitro and in vivo, probably by mechanisms similar to those identified in DIF-1 actions, and that DIF-3 may be a potential novel anti-cancer agent. |
