Expression of ErbB2
protein is inversely correlated with the prognosis in
cancer patients. Consequently, strategies targeting ErbB2 remain an attractive option in treating several types of
malignancies, including
oral cancer. In addition, many studies have shown that
emodin and
emodin derivatives are able to inhibit growth of ErbB2-overexpressing
tumor cells. In this study, a series of computer modeling-generated
emodin analogues were synthesized and tested for their antiproliferative activity against
oral cancer cell lines overexpressing ErbB2. Among these analogues, em08red (1,8-dihydroxy-9(10H)-anthracenone) demonstrated potent antiproliferative activity against all three tested ErbB2-overexpressing cell lines, ie, FaDu, HSC3, and OECM1. Treatment with em08red significantly downregulated activation of ErbB2 as well as the ErbB2
protein expression level in the tested cell lines and induced G2 arrest. Antiapoptosis
protein (Bcl-xl and Bcl-2) expression levels were also downregulated, and active
caspase-3 and
caspase-9 was detected in cells
after treatment with em08red. Moreover, treatment with em08red stimulated production of cytotoxic
reactive oxygen species in treated cells, and this could be partially reversed by pretreatment with
N-acetylcysteine. Overall, we demonstrated inhibition of ErbB2 function and induction of
reactive oxygen species in
tumor cells by em08red, which prevented proliferation of
tumor cells and induced apoptotic cell death.