Curcumin: Modulator of Key Molecular Signaling Pathways in Hormone-Independent Breast Cancer

Abstract

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among women worldwide. Despite the overall successes in breast cancer therapy, hormone-independent HER2 negative breast cancer, also known as triple negative breast cancer (TNBC), lacking estrogens and progesterone receptors and with an excessive expression of human epidermal growth factor receptor 2 (HER2), along with the hormone-independent HER2 positive subtype, still remain major challenges in breast cancer treatment. Due to their poor prognoses, aggressive phenotype, and highly metastasis features, new alternative therapies have become an urgent clinical need. One of the most noteworthy phytochemicals, curcumin, has attracted enormous attention as a promising drug candidate in breast cancer prevention and treatment due to its multi-targeting effect. Curcumin interrupts major stages of tumorigenesis including cell proliferation, survival, angiogenesis, and metastasis in hormone-independent breast cancer through the modulation of multiple signaling pathways. The current review has highlighted the anticancer activity of curcumin in hormone-independent breast cancer via focusing on its impact on key signaling pathways including the PI3K/Akt/mTOR pathway, JAK/STAT pathway, MAPK pathway, NF-ĸB pathway, p53 pathway, and Wnt/β-catenin, as well as apoptotic and cell cycle pathways. Besides, its therapeutic implications in clinical trials are here presented.

Development of a Prognostic Model Based on the Identification of EMT-Related lncRNAs in Triple-Negative Breast Cancer

“…Among the enriched pathways, some of them had been clarified to play critical roles in TNBC development. For example, the P53 pathway can induce the transcription of target genes responsible for various cellular mechanisms (mainly DNA repair) and activate diverse forms of stimuli (such as hypoxia), which are consistent with our enrichment results [ 19 ]. It is widely acknowledged that the loss of P53 function may lead to deficiency in cell cycle checkpoint, genome instability, cellular immortalization, and excessive cell proliferation [ 20 , 21 ].…”

Nutraceuticals and Cancer: Potential for Natural Polyphenols

“…The proinflammatory transcription factor NF-κB regulates more than 500 different genes expressing for proteins involved in cellular signaling pathways, so all compounds that interact with NF-κB, inhibiting it, may be used in cancer therapy. Curcumin was able to downregulate NF-κB in breast cancer cells [161] and played an important role in hematologic tumors: in leukemia, curcumin stopped nuclear translocation of NF-κB and the degradation of human myeloid ML-1a cells [162]; moreover, curcumin triggered apoptotic death in B-cell chronic lymphocytic leukemia (CLL-B) by downregulation of the STAT3, AKT, and NF-κB proteins [163]. The treatment of gastric cancer indicated the pharmacological efficiency of curcumin, which inhibited antiapoptotic proteins of the Bcl-2 family and increased the expression of caspases 3, 8, 9, p53, and Bax [164].…”

Curcumin as an Enhancer of Therapeutic Efficiency of Chemotherapy Drugs in Breast Cancer

“…CUR exerts anti breast cancer impact through targeting various regulatory proteins, including those of kinases, transcription factors, receptors, enzymes, growth factors, cell cycle, and apoptosis-related molecules, as well as miroRNAs. It has also been shown to modulate a variety of key signaling pathways of JAK/STAT, NF-kB, Wnt/β-catenin, PI3K/Akt/mTOR, MAPK, apoptosis, and cell cycle pathways involved in breast cancer progression and development [20][21][22][23].…”