AIM: To investigate the effect of all-trans-retinoic acid (ATRA) on arsenic trioxide (As_2O_3)-induced apoptosis of human hepatoma, breast cancer, and lung cancer cells in an attempt to find a better combination therapy for solid tumors. METHODS: Human hepatoma cell lines HepG2, Hep3B, human breast cancer cell line MCF-7, and human lung adenocarcinoma cell line AGZY-83-a were treated with As_2O_3 together with ATRA. Cell survival fraction was determined by MTT assay, cell viability and apoptosis were measured by annexin V-fluorescein isothiocyanate (FITC) and PI staining, and intracellular glutathione (GSH) and glutathione-S-transferase (GST) activities were determined using commercial kits. RESULTS: Cytotoxicity of ATRA was low. ATRA (0.1, 1, and 10 umol/L) could synergistically potentiate As_2O_3 to exert a dose-dependent inhibition of growth and to induce apoptosis in each of the cell lines. HepG2 and Hep3B with low intracellular GSH or GST activities were remarkably sensitive to As_2O_3 or As_2O_3+ATRA, while AGZY-83-a with higher GSH or GST activities was less sensitive to As_2O_3 or As_2O_ 3+ATRA. Treatment with 2 umol/L As_2O_3 for 72 h significantly decreased intracellular GSH and GST levels in each of the cell lines, and 1 umol/L ATRA alone reduced minimal intracellular GSH and GST levels. ATRA potentiated the effect of As_2O_3 on intracellular GSH levels, but intracellular GST levels were not significantly affected by the combination of As_2O_3 and ATRA for 72 h as compared to As_2O_3 alone. CONCLUSION: ATRA can strongly potentiate As_2O_3-induced growth-inhibition and apoptosis in each of the cell lines, and two drugs can produce a significant synergic effect. The sensitivity to As_2O3_ or As_2O_3+ATRA is inversely proportional to intracellular GSH or GST levels in each of the cell lines. The GSH redox system may be the possible mechanism by which ATRA synergisticaily potentiates As_2O_3 to exert a dose-dependent inhibition of growth and to induce apoptosis. AIM: To investigate the effect of all-trans-retinoic acid (ATRA) on arsenic trioxide (As 2 O 3) -induced apoptosis of human hepatoma, breast cancer, and lung cancer cells in an attempt to find a better combination therapy for solid tumors. METHODS : Human hepatoma cell lines HepG2, Hep3B, human breast cancer cell line MCF-7, and human lung adenocarcinoma cell line AGZY-83-a were treated with As_2O_3 together with ATRA. Cell survival fraction was determined by MTT assay, cell viability and apoptosis RESULTS: Cytotoxicity of ATRA was low. ATRA (0.1, 1) was measured by annexin V-fluorescein isothiocyanate (FITC) and PI staining, and intracellular glutathione (GSH) and glutathione- S-transferase (GST) activities were measured using commercial kits. , and 10 umol / L) could synergistically potentiate As_2O_3 to exert a dose-dependent inhibition of growth and to induce apoptosis in each of the cell lines. HepG2 and Hep3B with low intracellular GSH or GST activities were remarkably sensitive to As While either AGZY-83-a with higher GSH or GST activities was less sensitive to As_2O_3 or As_2O_3 + ATRA. Treatment with 2 umol / L As_2O_3 for 72 h significantly decreased intracellular GSH and GST levels in each of the cell lines, and 1 umol / L ATRA alone reduced minimal intracellular GSH and GST levels. ATRA potentiated the effect of As 2 O 3 on intracellular GSH levels, but intracellular GST levels were not significantly affected by the combination of As 2 O 3 and ATRA for 72 h as compared to As_2O_3 alone. CONCLUSION: ATRA can strongly potentiate As_2O_3-induced growth-inhibition and apoptosis in each of the cell lines, and two drugs can produce a significant synergic effect. The sensitivity to As_2O_3_ or As_2O_3 + ATRA is inversely proportional to intracellular GSH or GST levels in each of the cell lines. The GSH redox system may be the possible mechanism by which ATRA synergisticaily potentiates As_2O_3 to exert a dose-dependent inhibition of growth and to induced apoptosis