A novel indole-3-carbinol derivative inhibits the growth of human oral squamous cell carcinoma in vitro.
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.
Weng
Jing-Ru
JR
Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan. columnster@gmail.com
Bai
Li-Yuan
LY
Omar
Hany A
HA
Sargeant
Aaron M
AM
Yeh
Ching-Tung
CT
Chen
Yuan-Yin
YY
Tsai
Ming-Hsui
MH
Chiu
Chang-Fang
CF
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
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