MOLECULAR MECHANISTIC AND BIOINFORMATICS PERSPECTIVES ON CURCUMIN FROM CURCUMA LONGA IN BREAST CANCER THERAPY

Abstract

Breast cancer is one of the most important causes of cancer deaths around the world, and new strategies for treatment are urgently required that overcome tumor heterogeneity as well as treatment resistance. Curcumin, the main bioactive polyphenol compound of Curcuma longa, is becoming a promising anticancer agent because it exhibits pleiotropic molecular activities on several oncogenic pathways. This review aims to give a complete synthesis of curcumin therapeutic benefits in breast cancer in the light of molecular mechanisms, as well as bioinformatics and multi-omics approaches. Curcumin's anticancer properties include the modulation of cell proliferation, induction of apoptosis, modulation of autophagy, inhibition of migration and metastasis, and epigenetic actions, such as DNA methylation, histone modifications and non coding RNAs. Curcumin directly blocks the phosphorylation of STAT3, thus blocking its movement from cytoplasm to nucleus and blocking its DNA-binding activity, and consequently preventing tumor proliferation and survival. Alters important signaling pathways, such as PI3K/AKT/mTOR, MAPK/ERK, JAK/STAT, NF-κB and Wnt/β-catenin pathways. Bioinformatics has revealed that curcumin targets the molecular targets, AKT, TNF and TP53 with high affinity, and network pharmacology has helped reveal curcumin's multi-target mechanisms and protein interaction networks. The formulation of curcumin by liposomes has been shown to be more effective in the MCF-7 breast cancer cells, with the IC₅₀ decreasing from 19.81 ± 1.03 μg/mL to 9.16 ± 0.67 μg/mL. Although preclinical data are promising, the delivery of these drugs to the clinic has been limited by poor bioavailability, metabolism and absorption. In order to overcome these limitations, nanotechnology based delivery systems and combination strategies have been promising. Overall, this review sheds light on the potential of curcumin as a promising precision oncology drug, combining computational and experimental strategies to advance the treatment of breast cancer.