4-hexylresorcinol stimulates the differentiation of SCC-9 cells through             the suppression of E2F2, E2F3 and Sp3 expression and the promotion of Sp1 expression.
The dormancy-inducing factors of bacteria inhibit tumor cell growth. In             the present study, we evaluated the antitumor effects of the dormancy-inducing             factor 4-hexylresorcinol (4-HR) using real-time cell electronic sensing (RT-CES)             in SCC-9 cells (tongue squamous cell carcinoma cells). Treatment with 4-HR suppressed             the growth of SCC-9 cells in a dose-dependent manner. We used a DNA microarray             to identify genes that showed a significant change in expression upon 4-HR administration             in SCC-9 cells. Among the differentially expressed genes, the protein expression             of several cell proliferation related factors, including E2F1, E2F2, E2F3, E2F4,             E2F5, E2F6, Sp1 and Sp3, were determined by western blot analyses. Treatment with             4-HR strongly suppressed E2F2 and slightly suppressed E2F3 but did not change             the expression of E2F1, E2F4, E2F5 and E2F6 relative to no treatment. Furthermore,             4-HR increased Sp1 expression in a dose-dependent manner and decreased Sp3 expression.             Therefore, the ratio of Sp1 to Sp3, an important driving force of epithelial cell             differentiation, was drastically increased. Consistent with this observation,             4-HR increased the expression of the epithelial cell differentiation markers involucrin             and keratin 10. Together, our results indicate that 4-HR induces the differentiation             of SCC-9 via the modulation of the E2F-mediated signaling pathway.
Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University, Gangneung 210-702, Republic of Korea. epker@chollian.net
Seong-Gon
SG
Kim
An-Sook
AS
Kim
Jae-Hwan
JH
Jeong
Je-Yong
JY
Choi
Haeyong
H
Kweon
D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D050703:E2F2 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D050699:E2F3 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006604:Hexylresorcinol / Q000494:pharmacology*; D006801:Humans; D046228:Microarray Analysis; D015398:Signal Transduction / Q000187:drug effects; D016329:Sp1 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D051705:Sp3 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D014062:Tongue Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
D050703:E2F2 Transcription Factor; C493761:E2F2 protein, human; D050699:E2F3 Transcription Factor; C098319:E2F3 protein, human; C497121:SP3 protein, human; D016329:Sp1 Transcription Factor; D051705:Sp3 Transcription Factor; D006604:Hexylresorcinol