PMID: 15354410Sep 10, 2004Paper

Combined effect of arsenic trioxide and sulindac sulfide in A549 human lung cancer cells in vitro

Journal of Experimental & Clinical Cancer Research : CR
T T JiangJ H Kim

Abstract

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 re...Continue Reading

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