4-Hexylresorcinol Induced an Apoptosis and Differentiation of Oral Cancer Cells

Abstract

Statement: A chemical analog of natural alkylresorcinols, 4-hexylresorcinol (4-HR), is known to induce dormancy in bacteria for survival under extreme environments. However, it is not known if 4-HR has an antitumor effect. This study examined whether or not 4-HR has anti-tumor effect through apoptosis. Materials and Methods: SCC-9 was used for the cell culture and xenograft model. The effects of 4-HR on the cellular proliferation were examined by a MTT assay, TUNNEL assay, and immunocytochemistry. In the case of a xenograft model, SCC-9 was implanted subcutaneously, and 4-HR was administered by an intraperitoneal injection. The tumor size was measured periodically and the mass was examined by immunohistochemistry. Method of Data Analysis: n/a Results: 4-HR significantly suppressed the proliferation of SCC-9 cells in a dose-dependent manner along with the inhibition of respiratory activity (p 0.05). It also caused prominent morphological changes including size reduction and a rounding of the SCC-9 cells. Interestingly, 4-HR increased the expression of various differentiation markers, which was confirmed by proteomics analysis and RT-PCR. The 4-HR-mediated effects were due in part to an increase of intracellular calcium, which was demonstrated by confocal microscopy and immunocytochemistry. This might be a key mechanism for cellular apoptosis. An intraperitoneal injection of 4-HR substantially and dose-dependently reduced the tumor mass after the implantation of SCC-9 cells into the nude mice model (p 0.05). Immunochemical analysis showed increased cytokeratin expression, a well-known marker of epithelial cell differentiation. However, the level of Ki67 expression, a cellular proliferation marker, was decreased after the administration of 4-HR compared with the control. Conclusion: Overall, these results suggest that 4-HR has an anti-tumor effect through apoptosis and the reversion of de-differentiated tumor cells into more differentiated cells. Presence of Dominant-Negative p53 Mutation Is a Risk of Early Recurrence in Oral Squamous Cell Carcinoma Haruhiko Kashiwazaki, DDS, PhD, Kita-13 Nishi-7, Kitaku, Sapporo, Hokkaido, 060-8586, Japan (Yamazaki Y; Tei K; Kitagawa Y; Totsuka Y; Inoue N; Hassan N)