Multiple Myeloma Tumor Cells are Selectively Killed by Pharmacologically-dosed Ascorbic Acid

Highlights

• Pharmacologically-dosed ascorbic acid kills Multiple Myeloma cells.

• Pharmacologically-dosed ascorbic leads to apoptosis-inducing factor 1 cleavage.

• Pharmacologically-dosed ascorbic lowers melphalan dosage.

Multiple myeloma (MM) remains a difficult to cure disease in the majority of cases. Several preclinical and clinical studies have shown that ascorbic acid in pharmacologic doses (PAA) selectively kills cancer cells, while sparing normal cells. This article reveals the biological mechanism by which PAA exerts its anti-cancer effects and should lead to the development of an innovative therapy in MM.

Abstract

High-dose chemotherapies to treat multiple myeloma (MM) can be life-threatening due to toxicities to normal cells and there is a need to target only tumor cells and/or lower standard drug dosage without losing efficacy. We show that pharmacologically-dosed ascorbic acid (PAA), in the presence of iron, leads to the formation of highly reactive oxygen species (ROS) resulting in cell death. PAA selectively kills CD138⁺ MM tumor cells derived from MM and smoldering MM (SMM) but not from monoclonal gammopathy undetermined significance (MGUS) patients. PAA alone or in combination with melphalan inhibits tumor formation in MM xenograft mice. This study shows PAA efficacy on primary cancer cells and cell lines in vitro and in vivo.