| 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. |
