Arsenic is naturally occurring toxic
metalloid and drinking As2 O3 containing water are recognized to be related to increased risk of neurotoxicity, liver injury, blackfoot disease,
hypertension, and
cancer. On the contrary, As2 O3 has been an ancient
drug used in
traditional Chinese medicine with substantial anticancer activities, especially in the treatment of
acute promyelocytic leukemia as well as chronic wound healing. However, the cytotoxicity and detail mechanisms of As2 O3 action in solid
cancer cells, such as
oral cancer cells, are largely unknown. In this study, we have primarily cultured four pairs of
tumor and nontumor cells from the
oral cancer patients and treated the cells with As2 O3 alone or combined with
dithiothreitol (DTT). The results showed that 0.5 μM As2 O3 plus 20 μM DTT caused a significant cell death of
oral cancer cells but not the nontumor cells. Also As2 O3 plus DTT upregulated Bax and Bak, downregulated Bcl-2 and p53, caused a loss of mitochondria membrane potential in
oral cancer cells. On the other way, As2 O3 also triggered endoplasmic reticulum stress and increased the levels of
glucose-regulated
protein 78,
calpain 1 and 2. Our results suggest that DTT could synergistically enhance the effects of As2 O3 on killing
oral cancer cells while nontoxic to the nontumor cells. The combination is promising for clinical practice in
oral cancer therapy and worth further investigations. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 17-27, 2017.