Abstract
(R)-(−)-xanthorrhizol is a bioactive sesquiterpenoid and major chemical constituent
of Curcuma zanthorrhiza rhizomes. It was reported to have many pharmacological activities
including nephroprotective, hepatoprotective, antimicrobial, anti-inflammatory, antioxidant,
antihypertensive, antihyperglycemic, antiplatelet, estrogenic, and antiestrogenic
properties. (R)-(−)-xanthorrhizol was also investigated for antiproliferative activity
against many cancer cells including breast, lung, liver, ovarian, and colon cancer.
It was also revealed to have a potential effect on TNBC cells MDA-MB-231. Considering
the previous studies, this study has aimed to investigate the antimigratory and anti-invasive
properties, as well as the possible molecular mechanisms, behind these properties.
The findings of (R)-(−)-xanthorrhizol on MDA-MB-231 cell migration and invasion demonstrated
significant inhibition at three different concentrations in a concentration-dependent
manner, which was observed
in the scratch, transwell migration, and invasion assays. Further investigation of
the molecular mechanism using gelatin zymography revealed that (R)-(−)-xanthorrhizol
prevented cell migration and invasion of breast cancer cells through the inhibition
of matrix metalloproteinase-2 and matrix metalloproteinase-9 expression. Western blot
analysis indicated that the inhibition of matrix metalloproteinases is possibly the
result of the inhibition of phosphorylation in the NF-κ B signaling pathway. These findings corroborate (R)-(−)-xanthorrhizol to proceed for
the further studies as a possible future drug candidate for cancer patients.
Keywords (R)-(−)-xanthorrhizol - Zingiberaceae -
Curcuma zanthorrhiza , antimigratory and anti-invasive - TNBC cells MDA-MB-231 - matrix metalloproteinases
- NF-
κ B signaling pathway