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Bruceantin inhibits multiple myeloma cancer stem cell proliferation
#MMPMID27434731
Issa ME
; Berndt S
; Carpentier G
; Pezzuto JM
; Cuendet M
Cancer Biol Ther
2016[Sep]; 17
(9
): 966-75
PMID27434731
show ga
Multiple myeloma (MM) continues to claim the lives of a majority of patients. MM
cancer stem cells (CSCs) have been demonstrated to sustain tumor growth. Due to
their ability to self-renew and to express detoxifying enzymes and efflux
transporters, MM-CSCs are rendered highly resistant to conventional therapies.
Therefore, managing MM-CSCs characteristics could have profound clinical
implications. Bruceantin (BCT) is a natural product previously demonstrated to
inhibit the growth of MM in RPMI 8226 cells-inoculated mouse xenograft models,
and to cause regression in already established tumors. The objectives of the
present study were to test the inhibitory effects of BCT on MM-CSCs growth
derived from a human primary tumor, and to explore a mechanism of action
underlying these effects. BCT exhibited potent antiproliferative activity in
MM-CSCs starting at 25 nM. BCT induced cell cycle arrest, cell death and
apoptosis in MM-CSCs as well as inhibited cell migration and angiogenesis in
vitro. Using a qPCR screen, it was found that the gene expression of a number of
Notch pathway members was altered. Pretreatment of MM-CSCs with the ?-secretase
inhibitor RO4929097, a Notch pathway inhibitor, reversed BCT-induced effects on
MM-CSCs proliferation. In this study, BCT was shown to be an effective agent in
controlling the proliferation, viability and migration of MM-CSCs as well as
angiogenesis in vitro. The effect on MM-CSCs proliferation may be mediated by the
Notch pathway. These results warrant further investigation of BCT in a broader
set of human-derived MM-CSCs and with in vivo models representative of MM.
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