Potential of Nitrostyrene Compounds in CLL
Posted: Thursday, August 1, 2019
According to Sandra A. Bright, PhD, and colleagues, of Trinity College in Dublin, nitrostyrene compounds can induce apoptosis in chronic lymphocytic leukemia (CLL) cells. The nitrostyrene scaffold, based on the structure of the amphetamine analog, 4-MTA (4-methylthioamphetamine), had previously formed the basis for development of compounds targeting Burkitt’s lymphoma. The authors, who published their findings in Oncology Reports, investigated whether these compounds could likewise target CLL.
In this study, the authors assessed the effect of three representative nitrostyrene compounds (1, 2, and 3) on cell viability using flow cytometry, alamar blue, and lactate dehydrogenase assays, as well as drug-interaction analyses. Among others, 4 CLL cell lines, representative of “poor” (CII and HG-3) and “good” CLL prognoses (I83 and PGA-1) were included for testing. Peripheral blood samples from 14 patients with CLL were also used in ex vivo experiments.
Compounds 1 and 2 reduced cell viability more than comparators (fludarabine phosphate and paclitaxel) in all 4 CLL cell types tested. Nitrostyrene-induced apoptosis was dependent on caspase and reactive oxygen species. Co-treatment of HG-3 and PGA-1 cells with idelalisib increased the rate of apoptosis over treatment with either compound 1 or 2 alone. Apoptosis was also increased in cells co-cultured with bone marrow stromal HS5 cells and either compound 1 or 2. The effect was similar in ex vivo CLL cells, including those belonging to patients with poor clinical markers.
Disclosure: The study authors’ disclosure information may be found at spandidos-publications.com.