4-hexylresorcinol exerts antitumor effects via suppression of calcium oscillation and its antitumor effects are inhibited by calcium channel blockers

The Bacterial dormancy-inducing factor 4-hexylresorcinol (4-HR) has been shown to have synergistic antitumor effects when used in combination with cisplatin. In the present study, 4-HR was used as a single agent in the squamous carcinoma cell line SCC-9. The results demonstrated that 4-HR suppressed SCC-9 cell proliferation compared to primary cultured gingival fibroblasts. 4-HR dose-dependently induced SCC-9 cell Apoptosis as determined by Caspase-3 activity, annexin V expression, as well as by scanning and transmission electron microscopy. 4-HR inhibited intracellular calcium oscillation in both SCC-9 cells and normal human dermal fibroblasts. 4-HR-induced Apoptosis was partly reversed by Calcium Channel blockers. Of note, 4-HR reduced the tumor mass formed by SSC-9 cell implantation in BALB/cAnNCrj-nu/nu mice and mass size reduction was also partly reversed by the concomitant application of Calcium Channel blockers. Collectively, our results suggest that 4-HR has strong antitumor effects by inhibiting Calcium Channel oscillation and inducing Apoptosis.