The alteration of mitochondria is an early event of arsenic trioxide induced apoptosis in esophageal carcinoma cells

It is accepted that inorganic arsenic trioxide is an inducer of apoptosis f or many types of cancer. Our previous studies have demonstrated that arseni c trioxide induces apoptosis of esophageal carcinoma cells. Administration of arsenic trioxide results in the inhibition of growth and survival of tum or cells. Esophageal carcinoma cells treated with arsenic trioxide for 3 da ys demonstrated a typical morphological appearance of apoptosis, To further examine molecular mechanism of arsenic trioxide induced apoptosis of esoph ageal carcinoma cells, we have investigated the early changes of the apopto tic cell induced by arsenic trioxide. Our results indicated that arsenic tr ioxide induced apoptosis of esophageal carcinoma cells occurs as early as 2 h after treatment. Annexin-v staining has further proved that the phosphat idylserine is exposed at 2 h. The ear-ly morphological change of arsenic tr ioxide treated cells was in the mitochondria. Arsenic trioxide treated cell s displayed aggregated mitochondria. It induces accumulation of high electr on-density amorphous substances, swollen and disruption of mitochondria in oesophageal carcinoma cells after 2 h treatment. The alteration of mitochon dria induced by arsenic trioxide seems to occur before the condensation of chromatin. Thus, our data demonstrated that the primary target of arsenic t rioxide induced apoptosis of esophageal carcinoma cells may be the mitochon dria. It is possible that arsenic trioxide is a mitochondriotoxic agent.