4-hexylresorcinol stimulates the differentiation of SCC-9 cells through the suppression of E2F2, E2F3 and Sp3 expression and the promotion of Sp1 expression

• Published in: Oncology reports Vol. 28; no. 2; pp. 677 - 681
• Main Authors: KIM, SEONG-GON, KIM, AN-SOOK, JEONG, JAE-HWAN, CHOI, JE-YONG, KWEON, HAEYONG
• Format: Journal Article
• Language: English
• Published: Athens D.A. Spandidos 01.08.2012; Spandidos; Spandidos Publications UK Ltd
• Subjects: 4-hexylresorcinol; Apoptosis; Biological and medical sciences; Biotechnology; Cancer therapies; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cell cycle; Cell Differentiation - drug effects; Cell growth; Cell Growth Processes - drug effects; Cell Line, Tumor; Deoxyribonucleic acid; differentiation; DNA; E2F; E2F2 Transcription Factor - biosynthesis; E2F2 Transcription Factor - genetics; E2F3 Transcription Factor - biosynthesis; E2F3 Transcription Factor - genetics; Gene Expression - drug effects; Hexylresorcinol - pharmacology; Humans; Immunoglobulins; Keratin; Lipids; Medical sciences; Microarray Analysis; SCC-9 cells; Senescence; Signal Transduction - drug effects; Sp1 Transcription Factor - biosynthesis; Sp1 Transcription Factor - genetics; Sp3 Transcription Factor - biosynthesis; Sp3 Transcription Factor - genetics; Studies; Tongue Neoplasms - genetics; Tongue Neoplasms - metabolism; Tongue Neoplasms - pathology; Transcription factors; Tumors; United States > US; Hexylresorcinol; Transcription factor Sp1; Cancerology; Transcription factor Sp3; differentiation; 4-hexylresorcinol; Transcription factor E2F; E2F; Cell differentiation; SCC-9 cells
• ISSN: 1021-335X; 1791-2431
• DOI: 10.3892/or.2012.1845

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.