Curcumin for Treating Breast Cancer: A Review of Molecular Mechanisms, Combinations with Anticancer Drugs, and Nanosystems

Abstract

Breast cancer (BC) has become the fifth most prevalent cause of cancer-related morbidity, attracting significant attention from researchers due to its heightened malignancy and drug resistance. Conventional chemotherapy approaches have proven inadequate in addressing all BC subtypes, highlighting the urgent need for novel therapeutic approaches or drugs. Curcumin (CUR), a phytochemical derived from Curcuma longa (turmeric), has shown substantial potential in inhibiting BC cell migration, metastasis, and proliferation. However, the use of CUR in this context comes with challenges due to its dynamic and easily degradable nature, poor aqueous solubility, low bioavailability, rapid metabolism, and swift systemic elimination, collectively limiting its clinical applications. As such, we provide an overview of the properties, synthesis, and characterization of the hybridization of CUR and its analogue with chemo-drug building blocks. We reviewed research from the last five years on CUR's biogenesis with respect to the regulation of BC, revealing that CUR participates in arresting BC cells in the cell cycle and significantly induces apoptosis in BC cells. Information on the chemotherapeutic and antitumor mechanisms of CUR in BC, including regulation of the cell cycle, increased cell apoptosis, and inhibition of multidrug resistance (MDR), was compiled. Additionally, we provide an overview of CUR loaded into nanomaterials that are cotreated with other chemotherapeutic drugs, such as paclitaxel, thymoquinone, and tamoxifen. In this review, we discuss different types of nanoparticles that can be used for CUR delivery, such as polymeric nanoparticles, carbon nanotubes, and liposomes. By comparing the size, entrapment efficiency, drug-loading capacity, release time, biocompatibility, pharmaceutical scale, and reproducibility of various nanomaterials, we aimed to determine which formulations are better suited for loading CUR or its analogue. Ultimately, this review is expected to offer inspiring ideas, promising strategies, and potential pathways for developing advanced anti-BC strategy nanosystems in clinical practice.

Keywords: breast cancer; curcumin; drug delivery; nanosystems.

Figure 1

Chemical structure of curcumin (CUR).

Figure 2

The role of curcumin in cell-cycle regulation: CUR induces cell-cycle arrest in BC cells. The cell cycle is an ordered set of events that leads to cell growth and division (G1, S, and G2 phases).

Figure 3

The role of curcumin in apoptosis regulation: CUR induces apoptosis in BC cells, especially by activating P53 and P21 proteins to regulate the molecular targets of curcumin in breast cancer, which activates the PI3K-AKT, NF-kB, P53, and p21 signaling pathways. On the other hand, it induces ROS-mediated activation of typical P53 and JNK signaling pathways.

Figure 4

Nanodelivery systems in BC clinical treatments with CUR and its analogues. CUR and its analogues were delivered via different platforms. This activates several signaling pathways and target molecules. Phosphoinositide 3-kinases (PI3Ks); protein kinase B (Akt); B-cell lymphoma 2 (Bcl-2); epidermal growth factor receptor (EGFR); cyclin-dependent kinase inhibitor (CDK); vascular endothelial growth factor (VEGF); matrix metalloproteinases (MMP); extracellular signal-regulated kinases (ERKs); nuclear factor kappa-light chain enhancer of activated B cells (NF-κB); poly (ADP-ribose) polymerase (PARP); downregulated targets; upregulated targets.