Curcumin and its derivatives in breast cancer: Current developments and potential for the treatment of drug-resistant cancers

Abstract

Curcumin, a spice found in curry powder, is receiving considerable attention as a possible chemopreventative and chemotherapeutic. This review considers the evidence for the use of curcumin as a treatment for breast cancer, particularly triple negative breast cancers (lacking ER, PR and HER2) which are resistant to many current treatments. Evidence suggests that curcumin suppresses the growth of breast cancers both in vitro and in vivo. In ER-cell lines curcumin causes apoptosis via a range of mechanisms at concentrations ranging between 1 µM and 7.6 µM depending on the cell line and system. In xenograft models, curcumin has been shown to be effective but is limited by its bioavailability. This can be improved by nanotechnologies such as micelles. Studies with micelles have shown that these systems increase the uptake and cytotoxicity of curcumin in vitro. In xenotransplantation models micelles improved bioavailability and increased the half-life of curcumin while showing increases in apoptosis in implanted tumours. The last area discussed is the development of curcumin derivatives. Many of these show increased cytotoxicity (less than 1 µM) and improved pharmacokinetic profiles in vivo. The most potent of these compounds developed to date are RL66 and RL71 with IC 50 values less than 1 µM across a range of breast cancer cell lines, decreased metastasis in a xenograft model, decreased angiogenesis markers and improved tumour growth inhibition as compared to curcumin. Overall, this review concludes that curcumin and its derivatives show future potential as a powerful broad-spectrum treatment for breast cancer.

Evaluation of Curcumin Capped Copper Nanoparticles as Possible Inhibitors of Human Breast Cancer Cells and Angiogenesis: a Comparative Study with Native Curcumin

“…The central diketones form stable enols or are easily deprotonated and form enolates, while the α-and β-unsaturated carbonyl is a Michael acceptor and (19). The phenolic methoxy groups, as well as the ketone and enol groups, present on the ends and in the middle of the molecule, respectively, can participate in strong hydrogen bonding interactions (57).…”

Eliminating the Heart from the Curcumin Molecule: Monocarbonyl Curcumin Mimics (MACs)

“…Curcumin is, of course, the exception. A recent review on breast cancer by Cridge, Larsen and Rosengren summarizes associated molecular targets and points out the intervention of cytokines, growth factors, apoptosis and cell cycle proteins in addition to transcription factors and enzymes for a subset of MACs [ 32 ]. A recent modest kinase screen demonstrated that one MAC, EF31 ( 7a = 14 , X = NH, Y = N, Figure 2 ), is able to block 22 of 50 cancer-related kinases and suggests a mechanism dominated by competition with ATP [ 26 ].…”

“…Other reasons for turning from 1 to MACs are ease of synthesis [ 22 , 23 ] selectivity [ 9 , 24 , 25 ] and recognition that the pleiotropic nature [ 26 ] of the curcumin-like architecture permits rapid evaluation of drug potential for currently troublesome disorders such as highly resistant bacteria, Alzheimer’s syndrome, HIV, tuberculosis, malaria and diabetes [ 22 , 27 ]. Several excellent reviews detailing the diversity, applications and biological foundations of MACs for utility in human disease have appeared in the recent past [ 10 , 22 , 27 , 28 , 29 , 30 , 31 , 32 ].…”

Evaluation of the Effects of Aminonaphthoquinone Derivatives in Combination with Curcumin Against ER-positive Breast Cancer and Related Tumours

“…Besides being used as an adjuvant in breast cancer chemotherapy, curcumin is able to regulate many signalling targets and has been used to augment targeted therapy sensitization (17). The therapeutic benefit of curcumin as a clinical drug, however, remains a challenge due to its poor bioavailability (18,19). Various concerns have been raised regarding the efficacy of curcumin against cancer (20)(21)(22).…”