Opposite effects of arsenic trioxide on the Nrf2 pathway in oral squamous cell carcinoma in vitro and in vivo

Xinyan Zhang, Ying Su, Min Zhang, Zheng Sun
Cancer Letters 2012 May 1, 318 (1): 93-8
Nuclear factor erythroid derived 2 like 2 (Nrf2) is a critical transcriptional factor in mediating cellular defense mechanisms against oxidative stress or electrophiles. Arsenic has been reported to induce malignant transformation of human cells through Nrf2-dependent signaling pathway. However, arsenic is also a promising cancer therapeutic drug for solid tumors, including oral squamous cell carcinoma (OSCC). It is still unclear how Nrf2 may mediate cellular response of OSCC cells when treated with arsenic. In order to fully understand the impact of arsenic on Nrf2 signaling in human OSCC, we examined expression of Nrf2 and Nrf2-regulated genes in arsenic trioxide (ATO)-treated OSCC cells in vitro and in ATO-treated OSCC xenografts. ATO had anti-cancer effects on both cultured OSCC cells and OSCC xenografts by inhibiting cell growth, suppressing angiogenesis and inducing apoptosis. ATO activated a silent Nrf2 pathway in cultured OSCC cells as shown by induction of Nrf2 and Nrf2-regulated genes, NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1), in a dose-dependent manner. On the contrary, Nrf2 pathway became active in OSCC xenograft tumors, and ATO treatment down-regulated expression of Nrf2 and Nrf2-regulated genes. Our study clearly demonstrated opposite effects of ATO on Nrf2 pathway in OSCC cells in vitro and in vivo.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"