Breast cancer remains one of the leading causes of
cancer related deaths in women worldwide.
Bharangin is a
diterpenoid quinonemethide that has demonstrated therapeutic potential against
leukemia,
lymphoma, and
multiple myeloma cells. Whether this
diterpenoid exhibit activities against
breast cancer cells and the underlying mechanism is largely unknown. Herein, we provide evidence that
bharangin suppresses the proliferation of MCF-7, MDA-MB-231, MDA-MB-453, MDA-MB-468 and T-47D
breast cancer cells. As examined by AO/PI staining,
DAPI staining, sub-G1 analysis,
phosphatidylserine externalization,
caspase activation,
DNA laddering, and
poly-ADP ribose polymerase cleavage, the
diterpenoid induced apoptosis in
breast cancer cells. The growth inhibitory effect of
bharangin on
breast cancer cells was further confirmed from colony-formation assay. Furthermore, the
cancer cell migration was also suppressed by the
diterpenoid. Mechanistically,
bharangin was found to modulate multiple
cancer related cell signalling pathways in
breast cancer cells.
Bharangin suppressed the expression of cell survival and invasive
proteins, and induced Bax and mitochondrial depolarization in
breast cancer cells. The
diterpenoid also suppressed the activation of pro-inflammatory
transcription factor, nuclear factor (NF)-κB induced by
okadaic acid. Finally, the
diterpenoid induced the expression of
tumor suppressor lncRNAs (MEG-3, GAS-5), while down-regulating oncogenic H19 expression. Overall, these results suggest that
bharangin exhibits anti-carcinogenic, anti-proliferative and anti-inflammatory activities against
breast cancer cells. The modulation of
lncRNA expression and inhibition of NF-κB activation by
bharangin may contribute to its anti-carcinogenic activities.