Background: The anti-cancer potential of curcumin, a natural NFκβ inhibitor, has been reported
extensively in breast, lung and other cancers. In vitro and in vivo studies indicate that the therapeutic
efficacy of curcumin is enhanced when formulated in a nanoparticulate carrier. However, the
mechanism of action of curcumin at the molecular level in the hypoxic tumour micro-environment is
not fully understood. Hence, the aim of our study was to investigate the mechanism of action of curcumin
formulated as nanoparticles in in vitro models of breast and lung cancer under an hypoxic microenvironment.
Methods: Biodegradable poly(lactic-co-glycolic acid) PLGA nanoparticles (NP), loaded with curcumin
(cur-PLGA-NP), were fabricated using a solvent evaporation technique to overcome solubility issues
and to facilitate intracellular curcumin delivery. Cytotoxicity of free curcumin and cur-PLGA-NP was
evaluated in MDA-MB-231 and A549 cell lines using migration, invasion and colony formation assays.
All treatments were performed under an hypoxic micro-environment and whole cell lysates from controls
and test groups were used to determine the expression of HIF-1α and p65 levels using ELISA
Results: A ten-fold increase in solubility, three-fold increase in anti-cancer activity and a significant
reduction in the levels of cellular HIF-1α and nuclear p65 (Rel A) were observed for cur-PLGA-NP,
when compared to free curcumin.
Conclusion: Our findings indicate that curcumin can effectively lower the elevated levels of HIF-1α
and nuclear p65 (Rel A) in breast and lung cancer cells under an hypoxic tumour micro-environment
when delivered in nanoparticulate form. This applied means of colloidal delivery could explain the
improved anti-cancer efficacy of curcumin and has further potential applications in enhancing the activity
of anti-cancer agents of low solubility.