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

Abstract

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 µM 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 Kv2.1 and Kv3.2. 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.

Curcumin: Modulator of Key Molecular Signaling Pathways in Hormone-Independent Breast Cancer

“…These effects were accompanied by the regulation of Bax, Bcl-2, p16, and p21 expression, which eventually led to apoptosis induction and cell cycle arrest [ 143 ]. In contrast, it has been reported that curcumin treatment decreases the expression level of p53 and phosphorylated p53 (S392, S15, S392) in MDA-MB-231, SKBR3 and EMT6 cells, representing the induction of p53- independent apoptosis in treated cells [ 108 , 144 , 145 , 146 , 147 ]. Moreover, it has been documented that Notch1 overexpression is correlated with a highly expressed mutant p53 (R280K) in MDA-MB-231 cells, in which mutant p53 acts as its transcriptional activator.…”

Letter to the Editor: Boron enhances the antiviral activity of the curcumin against SARS-CoV-2

“…Treatments against viral infections that enhance HO-1 include various anesthetics (isoflurane or sevoflurane), hemin, estrogen, statins, curcumin, resveratrol, and melatonin [ 32 ]. Therefore, HO-1 expression can be strongly induced by heme analogues, such as hemin and curcumin derivatives, such as boron–curcumin complexes [ 33 , 34 ].…”

Metal–Curcumin Complexes in Therapeutics: An Approach to Enhance Pharmacological Effects of Curcumin

“…In a mouse model, this complex was shown to enhance accumulation of curcumin in the pancreas, which further potentiated gemcitabine-induced tumor growth and metastasis reduction [74]. Moreover, an iron-curcumin complex was shown to induce apoptosis and inhibit invasion of breast cancer cells [75]. As metal generates electromagnetic fields, a curcumin loaded nanoparticle with Fe 3 O 4 was prepared and tested against leukemia HL-60 cells.…”