Synergistic antiproliferative effect of mechlorethamine and amyloid beta-peptide on the human lung cancer cell line H441

Abstract

Mechlorethamine (ME) is an antineoplastic agent which has been in clinical use for more than six decades. ME therapy is associated with high toxicity, and it is often in combination with other therapeutics. The use of additional antiproliferative agents could allow the use of ME at lower concentrations, which could lead to comparable therapeutic results, but with lower toxicity. Recent findings have shown that the amyloid β-peptide (Aβ) has antiproliferative properties toward the human cancer cell line, H441 among others. In this study, the cooperative antiproliferative effect of Aβ and ME on the human cell line, H441, isolated from papillary adenocarcinoma lung tissue, was measured. Cells were cultured for 72 hours under standard culturing conditions in growth media containing either Aβ (2 µM), a very low dose of ME (0.2 µM), or both agents combined. We observed a 48% decrease in cell proliferation when Aβ and ME were used simultaneously, compared to 30% and 33% when ME or Aβ, respectively, were used independently. The study demonstrates that the antiproliferative properties of Aβ can augment the anticancer effect of toxic chemotherapeutics such as ME when used at lower doses.