Abstract 2935: A novel HSP70 inhibitor demonstrates potent anti-myeloma activity

Abstract

Abstract Multiple myeloma (MM) is a hematological cancer characterized by clonal proliferation of malignant plasma cells that produce monoclonal immunoglobulin. Because they secrete excess amounts of immunoglobulins, MM cells are typically under proteotoxic stress and utilize multiple mechanisms including molecular chaperones to maintain protein homeostasis. The chaperone HSP70 (heat shock protein 70) is overexpressed in MM. Therefore, we sought to evaluate whether targeting HSP70 with a novel HSP70 inhibitor would have a therapeutic benefit in MM. Toward this end, a panel of human MM cells lines including H929, RPMI-8226, MY-5, U266 and MM1s were tested for the IC50 to PET-16, an HSP70 inhibitor. Treatment with PET-16 resulted in a significant decrease in the viability of all MM cells tested with an IC50 value range from 3.5-7.2uM as was determined by the Alamar Blue assay. Decreased MM cell viability after treatment with PET-16 was due to induction of cellular apoptosis as was determined by Annexin V binding assay using flow cytometry. Because MM cells typically exist under hypoxic conditions, and hypoxia is known to decrease the efficacy of some chemotherapeutic agents, we analyzed the efficacy of PET-16 under hypoxia (1% oxygen). There was no difference in anti-MM effect of PET-16 in cells cultured under hypoxia as compared to those cultured in normoxic conditions. Taken together, our data suggest that targeting HSP70 with the novel HSP70 inhibitor PET-16 could be a viable potential strategy for treatment of MM. Citation Format: Charvann K. Bailey, Anna Budina, Maureen Murphy, Yulia Nefedova. A novel HSP70 inhibitor demonstrates potent anti-myeloma activity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2935. doi:10.1158/1538-7445.AM2015-2935