Ascorbic Acid Augments Arsenic-Mediated Cell Death in Multiple Myeloma (MM) Cells

. Greater than 90% of MM patients progress to a chemoresistant state (1). New therapies are clearly needed for the treatment of refractory MM that overcome or bypass the adaptive cellular changes associated with refractory disease: P-glycoprotein expression, increased Bcl-xL expression, elevated glutathione (GSH). Arsenic cytotoxicity is independent of Bcl-xL expression (2), making it a promising anti-neoplastic agent for MM. Ascorbic acid (AA) has recently been shown to deplete GSH via autooxidation and subsequent reduction reactions (3). Therefore, we hypothesized that the combination of arsenic and AA is likely to induce apoptosis in refractory MM cells.