Abstract: Objective To explore the effect of the Hsp90 inhibitor anacardic acid on cell proliferation, invasion and migration of
breast cancer MDA-MB-231 cells. Methods The inhibitory effect of anacardic acid on Hsp90 was assessed with in vitro ATPase
inhibition assay and ATP-sepharose binding assay. MTT assay was used to detect the growth inhibition induced by anacardic
acid in MDA-MB-231 cells. Transwell assays were used to evaluate MDA-MB-231 cell invasion and migration. Western blotting
was performed to assess the effect of anacardic acid in triggering the degradation of MMP-9, TIMP-1, Hsp90, and Hsp70.
Results Anacardic acid exhibited a modest activity of ATPase inhibition with an IC50 value of 82.5 μmol/L. Anacardic acid
significantly suppressed the proliferation of MDA-MB-231 cells in a dose-dependent manner (IC50 value of 29.3 μmol/L).
Treatment with 12.5, 25, and 50 μmol/L anacardic acid for 36 h caused inhibition of cell invasion by 23.6%, 56.6%, and 67.0% in
MDA-MB-231 cells, respectively (P<0.05), and anacardic acid treatment for 24 h inhibited the cell migration by 30.0%, 45.5%,
and 77.5%, respectively (P<0.05). Anacardic acid dose-dependently induced MMP-9 degradation, but did not obviously affect
Hsp90 or Hsp70 expressions. Conclusion Anacardic acid can significantly inhibit the proliferation, invasion, and migration of
MDA-MB-231 cells, the mechanism of which may involve the inhibition of Hsp90 ATPse activity and down-regulation of
MMP-9 expression.