Arsenic trioxide induces apoptosis of oesophageal carcinoma in vitro.

The arsenic compounds in traditional Chinese medicine have been recorded to have therapeutic effects on the treatment of psoriasis, syphilis, rheumatosis and a number of malignant tumours. Recent studies showed that arsenic trioxide can induce clinical remission in patients with acute promyelocytic leukemia, including those who have relapsed after retinoic acid treatment. however, the mechanism of how arsenic trioxide targets tumour cells is not clearly understood. We have examined the effects of arsenic trioxide on oesophageal carcinoma cell line EC8712. Our results demonstrated that the growth and survival of tumour cells were markedly inhibited by arsenic trioxide. The half dose effect (ED50) was at the concentration of 1 microM. Electron microscopic study demonstrated that EC8712 tumour cells treated with arsenic trioxide display a typical morphological appearance of apoptosis, including chromatin condensation and fragmentation of the nuclei. In contrast, no apoptotic features were observed in tumour cells without arsenic trioxide treatment. TUNEL assay also showed the biological features of apoptosis in cells treated with arsenic trioxide. Flow cytometry analyses showed that apoptotic peak was identified in arsenic trioxide treated cells but not in the control. Apoptotic cells in arsenic trioxide treated group account for 35% of total cell populations after three days treatment at a dose of 3 microM. In short, our results suggested that the anticancer effect of arsenic trioxide is due, at least in part, to the induction of apoptosis in cancer cells.