Abstract

Multiple myeloma (MM) is a cancer of plasma cells in the bone marrow characterized by bone lesions, hypercalcemia, anemia, and renal failure. Bortezomib (BTZ), a common treatment for MM, is a proteasome inhibitor that induces apoptosis in MM cells. However, high doses of BTZ can be toxic, signifying a need for a synergistic drug combination. Resveratrol (RES) is a phenolic compound found in grapes shown to inhibit MM cell growth and induce apoptosis in these cells. We hypothesize that combining BTZ with a RES derivative at certain concentrations is synergistic in reducing viability and inducing apoptosis in MM cells. To address this hypothesis, we performed viability assays to assess the effects of increasing concentrations of RES derivatives and BTZ on human MM cell viability over time (24, 48, 72 hours) and western blots to assess the compounds’ effects on inducing apoptosis in MM cells following 24 hour treatment. We found that BTZ as well as RES and its derivatives pinostilbene (PIN) and piceatannol (PIC) decreased MM cell viability in a dose‐ and time‐dependent manner and increased expression of cleaved proapoptotic proteins PARP1 and caspase‐3 in a dose‐dependent manner. We screened different combinations of RES derivatives with BTZ for synergistic effects on MM viability using CompuSyn and selected the combination of 5 nM BTZ and 5 μM PIN for further assessment as a synergistic treatment. In conclusion, a combination of low doses of BTZ and PIN synergistically decreases MM cell viability, possibly through inducing apoptosis.

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