Journal Article

Targeting STAT3 signaling pathway by curcumin and its analogues for breast cancer: A narrative review

Aghaei, Zeinab Hashem, Golmohammadi, Maryam, Jabbar, Thaer L., Jissir, Saad Abdul‐ridh, Hakimizadeh, Elham, Tahernia, Hossein, Kareem, Ali Kamil, Hjazi, Ahmed, Al‐Ani, Ahmed Muzahem, Zamanian, Mohammad Yassin

2024

Overview

Background Breast cancer (BC) continues to be a significant global health issue, with a rising number of cases requiring ongoing research and innovation in treatment strategies. Curcumin (CUR), a natural compound derived from Curcuma longa, and similar compounds have shown potential in targeting the STAT3 signaling pathway, which plays a crucial role in BC progression. Aims The aim of this study was to investigate the effects of curcumin and its analogues on BC based on cellular and molecular mechanisms. Materials & Methods The literature search conducted for this study involved utilizing the Scopus, ScienceDirect, PubMed, and Google Scholar databases in order to identify pertinent articles. Results This narrative review explores the potential of CUR and similar compounds in inhibiting STAT3 activation, thereby suppressing the proliferation of cancer cells, inducing apoptosis, and inhibiting metastasis. The review demonstrates that CUR directly inhibits the phosphorylation of STAT3, preventing its movement into the nucleus and its ability to bind to DNA, thereby hindering the survival and proliferation of cancer cells. CUR also enhances the effectiveness of other therapeutic agents and modulates the tumor microenvironment by affecting tumor‐associated macrophages (TAMs). CUR analogues, such as hydrazinocurcumin (HC), FLLL11, FLLL12, and GO‐Y030, show improved bioavailability and potency in inhibiting STAT3, resulting in reduced cell proliferation and increased apoptosis. Conclusion CUR and its analogues hold promise as effective adjuvant treatments for BC by targeting the STAT3 signaling pathway. These compounds provide new insights into the mechanisms of action of CUR and its potential to enhance the effectiveness of BC therapies. The figure is a graphical illustrating the effects of curcumin and its derivatives on various breast cancer cell lines, including MCF‐7, MCF10A, and MDA‐MB‐231 cells. Curcumin is shown to inhibit the proliferation of MDA‐MB‐231 cells and enhance the effects of IFN‐β/RA on breast cancer cells by up‐regulating GRIM‐19. It also inhibits STAT3 activation in MCF10A cells and increases the ratio of Bax to Bcl‐2 proteins while decreasing the activation of STAT3 in MCF‐7 cells. Hydrazino curcumin specifically inhibits STAT3 activation in MCF‐7 cells. Additionally, FLLL11 and FLLL12 inhibit AKT and STAT3 phosphorylation in breast cancer cells.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: adjuvants / Animals / Antineoplastic Agents - pharmacology / Antineoplastic Agents - therapeutic use / Apoptosis / Apoptosis - drug effects / Bioavailability / Bone cancer / Breast cancer / breast neoplasms / Breast Neoplasms - drug therapy / Breast Neoplasms - metabolism / Cancer therapies / Cell activation / Cell death / Cell growth / Cell migration / Cell proliferation / Cell Proliferation - drug effects / Cell survival / Colorectal cancer / Curcuma longa / Curcumin / Curcumin - analogs & derivatives / Curcumin - pharmacology / Curcumin - therapeutic use / curcumin analogues / DNA / Female / Humans / Macrophages / Mastectomy / Medical prognosis / medicine / Metastases / Metastasis / Molecular modelling / Nanomaterials / Nanoparticles / Phosphorylation / Public health / Regular / Review / Signal transduction / Signal Transduction - drug effects / Solvents / STAT3 / Stat3 protein / STAT3 Transcription Factor - metabolism / therapeutics / Tumor microenvironment / Tumors