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.
journal_name
Oral Oncoljournal_title
Oral oncologyauthors
Weng JR,Bai LY,Omar HA,Sargeant AM,Yeh CT,Chen YY,Tsai MH,Chiu CFdoi
10.1016/j.oraloncology.2010.08.005subject
Has Abstractpub_date
2010-10-01 00:00:00pages
748-54issue
10eissn
1368-8375issn
1879-0593pii
S1368-8375(10)00236-8journal_volume
46pub_type
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