Induction of apoptosis and inhibition of human gastric cancer MGC-803 cellgrowth by arsenic trioxide

Arsenic trioxide (As2O3), used to treat human diseases for centuries in tra ditional Chinese medicine, has been identified as a very effective antileuk aemic agent, but its effect on solid tumours which could be more suitable f or clinical treatment with arsenic compounds is still unknown. In this stud y, we investigated the in vitro effect of As2O3 at concentrations of 0.01-1 mu M against six human malignant cell lines, MGC-803, HIC, MCF-7, HeLa, BE L-7402 and A549 cells. As2O3 inhibited growth and induced apoptosis in thes e malignant cells at varying degrees, in a time dose-dependent manner. The most marked effects were seen in the gastric cancer cell line, MGC-803. In contrast, minimal growth inhibition and induction of apoptosis occurred in human embryonic pulmonary cells following treatment with As2O3 found at the same concentrations. Changes in intracellular Ca2+, following As2O3 treatm ent were measured by Ca2+ sensitive fluorescent probe Indo-1/AM in flow cyt ometric assays. The increase in intracellular Ca2+ correlated with the sens itivity of these cells to As2O3, possibly indicating that a critical intrac ellular Ca2+ signal transduction pathway could he involved in As2O3-mediate d cell-death and its selectivity. The marked sensitivity of MGC-803 cells i n vitro suggests that As2O3 may be a potential antigastric cancer agent. (C ) 1999 Elsevier Science Ltd. All rights reserved.