Effects of curcumin complexes on MDA-MB-231 breast cancer cell proliferation

摘要

Curcumin displays anticancer properties; however, some issues with the drug delivery mode limit its therapeutic use. Although reformulation and derivatization of curcumin have improved its bioavailability, curcumin derivatives may not retain the same anticancer properties as the parent compound. The present study investigated the anticancer properties of two curcumin complexes, the iron-curcumin [Fe(Cur) _(3)] and boron-curcumin [B(Cur) _(2)] complexes, in the MDA-MB-231 breast cancer cell line. The cellular localization of curcumin, B(Cur) _(2) and Fe(Cur) _(3) was determined by fluorescence microscopy. Cell proliferation, migration and invasion were also analysed. Furthermore, apoptosis-associated proteins were detected by using a proteome profiler array, and ion channel gene expression was analysed by reverse transcription-quantitative PCR. The results demonstrated that the three compounds were localized in the perinuclear and cytoplasmic regions of the cell, and displayed cytotoxicity with IC _(50) values of 25, 35 and 8 μ M for curcumin, B(Cur) _(2) and Fe(Cur) _(3), respectively. In addition, the three compounds inhibited cell invasion, whereas only curcumin and B(Cur) _(2) inhibited cell migration. Furthermore, cell exposure to curcumin resulted in an increase in the relative expression of the two key proapoptotic proteins, cytochrome c and cleaved caspase-3, as well as the antiapoptotic protein haem oxygenase-1. In addition, curcumin increased the expression levels of the voltage-gated potassium channels K v 2.1 and K v 3.2. Similarly, the expression levels of the chloride channel bestrophin-1 and the calcium channel coding gene calcium voltage-gated channel auxiliary subunit γ4 were increased following exposure to curcumin. Taken together, these results indicated that Fe(Cur) _(3) and B(Cur) _(2) may display similar anticancer properties as curcumin, suggesting that chemical complexation may be considered as a strategy for improving the potency of curcumin in the treatment of breast cancer.