BACKGROUND Natural compounds have been utilized in inhibiting
metastasis alone or in combination with other anti-
tumor agents.
Dehydrocostus lactone (DHC), a natural
sesquiterpene lactone, was used to investigate its effect on proliferation of
lung cancer cells and on the anti-angiogenic efficacy of
doxorubicin. MATERIAL AND METHODS Cell proliferation was assessed by MTT assay and clonogenic assay. Apoptosis and migration were assessed by flow cytometry and wound-healing assay, respectively. Western blotting and qPCR were performed for gene and
protein expression analysis.
Matrigel plug assay was performed for angiogenesis assessment. RESULTS Results of the study show that DHC inhibited the survival and proliferation of
lung cancer cells (A549 and H460) and enhanced the growth-inhibitory properties of DOX. Cotreatment of DHC enhanced the apoptosis-inducing effects of DOX by activating
caspase-9 and
caspase-3 followed by cleavage of PARP. Treatment of A549 and H460 cells with DHC caused suppression of HIF-1α, Akt and pAkt, GSK-3β and pGSK-3β, as well as ERK, pERK, mTOR, and p-mTOR. DHC enhanced the effect of DOX by inhibiting migration of A549 cells as observed by wound-healing assay. DHC caused synergistic inhibition of MMP-2 and MMP-9 genes when treated in combination with DOX. DHC further enhanced the anti-angiogenic properties of DOX in mice implanted with
Matrigel plugs. DHC suppressed the proliferation of
lung cancer cells and enhanced the anti-angiogenic properties of DOX. CONCLUSIONS The putative mechanism behind the
metastasis-limiting effects of DHC may involve the suppression of Akt/GSK-3β and inhibition of MMP-2 and MMP-9 in
lung cancer cells.