Curcumin as a chemotherapy compound for treatment of breast cancer

Introduction
Breast cancer is the most common malignant tumor among adult females, accounting for 30% of malignancy cases and 15% of cancer deaths in women. Major BCA subtypes include luminal A (MCF-7, T-47D), luminal B (BT-47, ZR-75-1), HER2-positive (HCCC-1954, SK-BR-3), and triple-negative breast cancer (TNBC) (MDA-MB-231, MDA-468, BI-549). Curcumin appears most effective in TNBC models, with MCF-7 cells being the second most responsive. Chemotherapy requires strict safety protocols including biological safety cabinets, personal protective equipment, and sterility maintenance. Curcumin's low water solubility and bioavailability are major challenges addressed through encapsulation and nanotechnology.

General Aspects
Chemical Structure of Curcumin
Curcumin (C₂₁H₂₀O₆, Mw 368.13 g/mol) is a natural phenolic pigment extracted from turmeric rhizome (Curcuma longa). It exists in enol-keto tautomeric forms—enol form soluble in organic solvents, keto form soluble in water. The diketone moiety regulates redox modulation activity and interacts with cellular proteins, while methoxy substitution enhances anticancer properties.

Properties of Curcumin
Curcumin is FDA-approved as GRAS, with antioxidant, anti-inflammatory, and cancer chemopreventive activities. It serves as a chemosensitizer in chemotherapy and photosensitizer in photodynamic therapy. Curcumin inhibits BCA cell migration, proliferation, adhesion, and invasion while triggering apoptosis. However, antioxidant supplements may reduce radiotherapy efficacy, and some studies associate antioxidant use during chemotherapy with increased recurrence risk.

Breast Cancer Epidemiology
GLOBOCAN 2022 data reported 2,296,840 new BCA cases worldwide (ASIR 46.8 per 10⁵) and 666,103 deaths (ASMR 12.7 per 10⁵). For patients under 40 years, there were 246,060 cases (ASIR 8.1) and 48,700 deaths (ASMR 1.6). BCA exhibits heterogeneity at genetic, epigenetic, transcriptomic, and proteomic levels.

Applications of Curcumin in Breast Cancer
Curcumin acts as an anticancer agent by causing G2/M phase cell cycle arrest, increasing apoptotic protein Bax, and decreasing proliferative proteins Akt-mTOR and anti-apoptotic BCL2. It activates ROS-signaling pathways and inhibits NF-κB and HER2. Molecular docking shows curcumin binds at TGFβ binding pockets via hydrogen bonds. Clinical trials with 8 g/day oral curcumin showed minimal plasma concentrations (~2.5 ng/mL) due to rapid metabolism. Combination therapies (curcumin with imatinib, docetaxel) showed enhanced efficacy.

Limitations, Challenges, and Solutions
Key limitations include low aqueous solubility, rapid metabolism, short half-life, and poor bioavailability. Piperine co-administration increases bioavailability by 2,000%. Other strategies include phospholipid complexes, liposomes, and nanotechnology-based encapsulation. Various nanoformulations have been developed: liposomes, polymeric nanoparticles, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), human serum albumin (HSA) nanoparticles, nanoemulsions, micelles, and carbon nanotubes.

Applications of Nanotechnology and Nano-Curcumin
Nano-curcumin at 80 mg/day for two weeks reduced radiation-induced skin reactions in BCA patients. Gum Arabic-curcumin micelles and alginate-curcumin-gold nanoparticles decreased MCF-7 cell viability. Protein Z-curcumin nanocomposites increased relative bioavailability by 305%. Lactoferrin-based ternary nanoparticles improved cellular uptake. Clinical studies demonstrate nano-curcumin inhibits tumor development, increases treatment efficacy, and reduces adverse effects.

Encapsulation of Curcumin
Encapsulation enhances stability and anticancer efficiency. HSA-curcumin nanoparticles conjugated with PDL1-binding peptides showed enhanced targeting to PDL1-expressing BCA cells. pH-sensitive carriers exploit pH differences between tumor tissues (pH 0.5-1 unit lower than normal) and cellular compartments (lysosomes pH 4.5-5, endosomes pH 5.5-6, cytosol pH 7.4). NLCs with mucoadhesive polymers (PEG 400, PVA, chitosan) improved oral delivery. Curcumin quantum dots in Eudragit RS 100 significantly inhibited BCA cells while sparing normal cells.

Research Gaps and Future Perspectives
Key gaps include: (1) disparity between basic research and therapeutic applications—solution: innovative techniques (gene editing, humanized mouse models, 3D bioprinting, patient-derived organoids); (2) lack of effective links between in vitro studies and clinical practice—solution: collaboration between researchers and clinicians; (3) large-scale production challenges—solution: advanced nanotechnology approaches; (4) safety concerns for nano-curcumin—solution: preclinical safety evaluation and dose optimization.

Conclusions
Curcumin is safe with antitumor properties, but low bioavailability necessitates high doses. Nano-curcumin is more effective than bulk form. Encapsulation enhances anticancer efficacy through slow, targeted release. Various nanoformulations (liposomes, lipid-based NPs, polymeric NPs, micelles, emulsions, metal-based NPs) improve absorption, provide controlled release, and protect against degradation. Encapsulated curcumin shows particular promise for TNBC treatment, though safety and efficacy must be confirmed through preclinical studies before clinical application.

Full text

https://www.xiahepublishing.com/2835-3315/CSP-2025-00022

The study was recently published in the Cancer Screening and Prevention.

Cancer Screening and Prevention (CSP) publishes high-quality research and review articles related to cancer screening and prevention. It aims to provide a platform for studies that develop innovative and creative strategies and precise models for screening, early detection, and prevention of various cancers. Studies on the integration of precision cancer prevention multiomics where cancer screening, early detection and prevention regimens can precisely reflect the risk of cancer from dissected genomic and environmental parameters are particularly welcome.

Follow us on X: @xiahepublishing

Follow us on LinkedIn:  Xia & He Publishing Inc.