Combined effect of arsenic trioxide and sulindac sulfide in A549 human lung cancer cells in vitro.
Arsenic trioxide has shown substantial efficacy in treating patients with relapsed or refractory acute promyelocytic leukemia (APL) as well as solid tumors. Arsenic can act through a considerable number of different pathways including mitochondrial respiration and tubulin formation, affecting growth, blood flow, differentiation, and apoptosis. Recent studies on the apoptotic potential of arsenic trioxide have elucidated some of its causal mechanisms, including elevation of intracellular H2O2, inhibition of NF-kappaB activity, and inhibition of GTP-induced polymerization of tubulin. Because of the variety in cellular approaches available to arsenic, it has been hypothesized that the combination of arsenic trioxide and other chemotherapeutic agents may result in cytotoxic synergy. Recent studies have proven this true, with all-trans retinoic acid, IFN-alpha, and ascorbic acid all yielding promising results when used in conjunction with arsenic trioxide. In this study we tested sulindac sulfide, a nonsteroidal anti-inflammatory drug (NSAID) to test its effects with arsenic. Sulindac was used because it functions by some of the same pathways as arsenic, including the mitochondrial apoptotic pathway and the NF-kappaB pathway. Our results show that sulindac sulfide enhances cytotoxicity when combined with arsenic trioxide, and that further studies on the exact mechanisms of their interaction are needed.
Jiang
T T
TT
Dept of Radiation Oncology, Henry Ford Health Sciences Center, Detroit, Michigan 48098, USA. ttj@umich.edu
Brown
S L
SL
Kim
J H
JH
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage; D006801:Humans; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000188:drug therapy*; D010087:Oxides / Q000008:administration & dosage; D013467:Sulindac / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D001152:Arsenicals; D010087:Oxides; D013467:Sulindac; C025462:sulindac sulfide; D000077237:Arsenic Trioxide