Cytotoxic Effects of Betel Quid and Areca Nut Aqueous Extracts on Mouse Fibroblast, Human Mouth-Ordinary-Epithelium 1 and Human Oral Squamous Cell Carcinoma Cell Lines.

BACKGROUND: Betel quid chewing is more common among the older generation in rural areas of Malaysia. Oral cancer in Asia has been associated with the habit of chewing betel quid and areca nut. OBJECTIVE:   This study aims to investigate the cytotoxic effects of betel quid and areca nut extracts on the fibroblast (L929), mouth-ordinary-epithelium 1 (MOE1) and oral squamous cell carcinoma (HSC-2) cell lines. METHODS: L929, MOE1 and HSC-2 cells were treated with 0.1, 0.2 and 0.4 g/ml of betel quid and areca nut extracts for 24, 48 and 72 h. MTT assay was performed to assess the cell viability. RESULTS: Both extracts, regardless of concentration, significantly reduced the cell viability of L929 compared with the control (P<0.05). Cell viability of MOE1 was significantly enhanced by all betel quid concentrations compared with the control (P<0.05). By contrast, 0.4 g/ml of areca nut extract significantly reduced the cell viability of MOE1 at 48 and 72 h of incubation. Cell viability of HSC-2 was significantly lowered by all areca nut extracts, but 0.4 g/ml of betel quid significantly increased the cell viability of HSC-2 (P<0.05). CONCLUSION: Areca nut extract is cytotoxic to L929 and HSC-2, whereas the lower concentrations of areca nut extract significantly increased the cell viability of MOE1 compared to the higher concentration and control group. Although betel quid extract is cytotoxic to L929, the same effect is not observed in MOE1 and HSC-2 cell lines. Further investigations are needed to clarify the mechanism of action.
.

Sall1, a causative gene for Townes-Brocks syndrome, enhances the canonical Wnt signaling by localizing to heterochromatin.

The Spalt (sal) gene family plays an important role in regulating developmental processes of many organisms. Mutations of human SALL1 cause the autosomal dominant disorder, Townes-Brocks syndrome (TBS), and result in ear, limb, anal, renal, and heart anomalies. Targeted deletion of mouse Sall1 results in kidney agenesis or severe dysgenesis. Molecular mechanisms of Sall1, however, have remained largely unknown. Here we report that Sall1 synergistically activates canonical Wnt signaling. The transcriptional activity of Sall1 is related to its nuclear localization to punctate nuclear foci (pericentromeric heterochromatin), but not to its localization or association with beta-catenin, the nuclear component of Wnt signaling. In contrast, the RNA interference of Sall1 reduces reporter activities of canonical Wnt signaling. The N-terminal truncated Sall1, produced by mutations often found in TBS, disturbs localization of native Sall1 to heterochromatin, and also down-regulates the synergistic transcriptional enhancement for Wnt signal by native Sall1. Thus, we propose a new mechanism for Wnt signaling activation, that is the heterochromatin localization of Sall1.