title: A novel indole-3-carbinol derivative inhibits the growth of human oral squamous cell carcinoma in vitro.
abstract: Indole-3-carbinol (I3C), a naturally occurring phytochemical found in cruciferous vegetables, has received much attention due to its translational potential in cancer prevention and therapy. In this study, we investigated the antitumor effects of OSU-A9, a structurally optimized I3C derivative, in a panel of oral squamous cell carcinoma cell lines, SCC4, SCC15, and SCC2095. The antiproliferative effect of OSU-A9 was approximately two-orders-of-magnitude higher than that of I3C. Importantly, normal human oral keratinocytes were less sensitive to OSU-A9 than oral cancer cells. This antiproliferative effect of OSU-A9 was attributable to the induction of mitochondrial-dependent apoptosis as evidenced by sub-G1 accumulation of cells, poly ADP-ribose polymerase cleavage, and cytochrome c release from the mitochondria. OSU-A9 down regulates Akt and NF-κB signaling pathways, leading to changes in many downstream effectors involved in regulating cell cycle and apoptosis. Moreover, the observed down regulation of IKKα and IKKβ expression by OSU-A9 is not reported for I3C. OSU-A9 also induces both the production of reactive oxygen species and the endoplasmic reticulum stress. Taken together, these results suggest the translational value of OSU-A9 in oral squamous cell cancer therapy in the future.
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan. columnster@gmail.com
authors.forename: Jing-Ru
authors.initials: JR
authors.lastname: Weng
authors.forename: Li-Yuan
authors.initials: LY
authors.lastname: Bai
authors.forename: Hany A
authors.initials: HA
authors.lastname: Omar
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Sargeant
authors.forename: Ching-Tung
authors.initials: CT
authors.lastname: Yeh
authors.forename: Yuan-Yin
authors.initials: YY
authors.lastname: Chen
authors.forename: Ming-Hsui
authors.initials: MH
authors.lastname: Tsai
authors.forename: Chang-Fang
authors.initials: CF
authors.lastname: Chiu
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D000432:Methanol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051379:Mice; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000378:metabolism
chemical_list: C523234:(1-(4-chloro-3-nitrobenzenesulfonyl)-1H-indol-3-yl)-methanol; D016588:Anticarcinogenic Agents; D018797:Cell Cycle Proteins; D007211:Indoles; D016159:Tumor Suppressor Protein p53; D000432:Methanol