Anticancer Activity of Guggulsterone in Multiple Myeloma Cells

Abstract

Guggulsterone (GS), a phytosteroid derived from guggul plants' gum resin, has anti-inflammatory and antioxidant properties. Although, the GS is found to have cytotoxic effects in Multiple Myeloma (MM) cells, the mechanisms of activity have not been described yet. Also, the GS-dependent expression of the High Mobility Group Box-1 (HMGB-1) protein, an attractive target for cancer therapy and its involvement in the JAK/STAT signaling pathway in MM is yet to be discovered. In this study, we aimed to investigate the anticancer activity of GS in various MM cell lines. GS treatment of MM cells resulted in inhibition of cell viability via loss of mitochondrial membrane potential, activation of caspases, and cleavage of Poly (ADP-ribose) polymerase (PARP). Moreover, GS downregulates the expression of HMGB-1 via JAK/STAT signaling pathway and suppresses the constitutive activation of the STAT3 signaling pathway. This study highlights the anticancer potential of GS in MM and the underlying molecular mechanisms responsible for its effect on the pathogenesis of this malignancy.