Opioids are a potential adjuvant treatment for certain
cancers; while they are primarily used to relieve
chronic pain, these drugs may also affect
cancer progression and recurrence.
Dezocine is one
opioid commonly used in China, but its effects on
cancer cells are unknown. Here, we demonstrated the inhibitory effect of
dezocine on
triple-negative breast cancer (TNBC) cells, and determined the underlying molecular mechanism. We found that
dezocine suppressed cell proliferation, migration and invasion, and induced apoptosis in TNBC cells. Xenograft models demonstrated the inhibitory effects of
dezocine treatment on TNBC
tumor growth in vivo. The anticancer effects of
dezocine were independent of
opioid receptors, which are not highly expressed by normal breast or
breast cancer tissues. A pull-down assay and LC-MS/MS analysis indicated that
dezocine directly targets NAMPT: computer modeling verified that the free energy of
dezocine kinetically bound into the pocket of NAMPT was -17.4 kcal/mol. Consequently,
dezocine treatment inhibited NAMPT
enzyme activity, resulting in cellular
NAD abolishment. We confirmed the
dezocine-induced inhibition of cell proliferation by both NAMPT knockdown and upon treatment with the inhibitor FK866. Our results suggest that both
dezocine and NAMPT might represent novel therapeutic targets for TNBC.