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 for many types of cancer. Our previous studies have demonstrated that arsenic trioxide induces apoptosis of esophageal carcinoma cells. Administration of arsenic trioxide results in the inhibition of growth and survival of tumor cells. Esophageal carcinoma cells treated with arsenic trioxide for 3 days demonstrated a typical morphological appearance of apoptosis. To further examine molecular mechanism of arsenic trioxide induced apoptosis of esophageal carcinoma cells, we have investigated the early changes of the apoptotic cell induced by arsenic trioxide. Our results indicated that arsenic trioxide induced apoptosis of esophageal carcinoma cells occurs as early as 2 h after treatment. Annexin-v staining has further proved that the phosphatidylserine is exposed at 2 h. The early morphological change of arsenic trioxide treated cells was in the mitochondria. Arsenic trioxide treated cells displayed aggregated mitochondria. It induces accumulation of high electron-density amorphous substances, swollen and disruption of mitochondria in oesophageal carcinoma cells after 2 h treatment. The alteration of mitochondria induced by arsenic trioxide seems to occur before the condensation of chromatin. Thus, our data demonstrated that the primary target of arsenic trioxide induced apoptosis of esophageal carcinoma cells may be the mitochondria. It is possible that arsenic trioxide is a mitochondriotoxic agent.
Shen
Z Y
ZY
Department of Pathology, Shantou University Medical College, Shantou 515031, P.R. China.
Shen
J
J
Cai
W J
WJ
Hong
C
C
Zheng
M H
MH
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D004938:Esophageal Neoplasms / Q000473:pathology / Q000648:ultrastructure; D005434:Flow Cytometry; D006801:Humans; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology; D010087:Oxides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D000077237:Arsenic Trioxide