Inhibition of Human Mantle Cell Lymphomas by the β2-Adrenergic Agonist, Levalbuterol, in the Hollow Fiber Assay in Mice

Abstract This study follows from the novel findings in our previous publication that β2-adrenergic receptor (β2AR) agonists show gene-expression signatures that are consistent with glucocorticoid receptor (GR) agonists. These observations were made with analytical software associated with the Harvard/MIT genomic database, CLUE. This formed a hypothesis that β2AR agonists would share the anti-inflammatory activity of GR agonists and their ability to induce apoptosis in tumors of lymphatic lineage. Our lead β2AR agonist from our previous study, levalbuterol, was tested for inhibitory activity upon 3 non-Hodgkin human cell lines, two of which were Mantle Cell carcinomas, JEKO-1 and MINO, and against SU-DHL-1, in mice: Species: Mus musculus; Strain: NMRI nude (Crl:NMRI-Foxn1nu), Sex: Females. The drug was supplied ad libitum in the drinking water at concentrations of 8 µg/ml and16 µg/ml over a period of 14 days. Statistically significant inhibition of lymphoma proliferation was observed at the higher concentration of levalbuterol. The data for the 3 cultures were combined to increase the power of the analysis. The average inhibition was 55 %, p <0.0001, consistent with the hypothesis that the β2AR agonist shared the apoptotic activity of the GR agonists with which it had similar gene-expression activity. Competing Interest Statement The authors have declared no competing interest.