ArticleThe Journal of nutritional biochemistry2019
Curcumin, but not curcumin-glucuronide, inhibits Smad signaling in TGFβ-dependent bone metastatic breast cancer cells and is enriched in bone compared to other tissues.
Article in The Journal of nutritional biochemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Targeting Mammalian 5-Lipoxygenase by Dietary Phenolics as an Anti-Inflammatory Mechanism: A Systematic Review.International journal of molecular sciences · 2021Pooled it
- Curcumin-based smart responsive hydrogels: A controlled release system for bone defect regeneration.Regenerative therapy · 2026Review
- Curcumin Inhibits Fibroblast Differentiation and Epithelial-Mesenchymal Transition to Alleviate Adenomyosis through TGF-β1/Smad3 Pathway.Chinese journal of integrative medicine · 2026Article
- Angiogenesis as a Therapeutic Target of (Poly)phenols: Tackling Cancer and Vascular-Related Complications.Molecular nutrition & food research · 2025Review
- Regulation of Curcumin on Follicle Initiation Rate in Diminished Ovarian Reserve.Combinatorial chemistry & high throughput screening · 2025Article
- The Function of the TGFβ Signaling Pathway in Connective Tissue Diseases: From Biology to Clinical Application.Journal of inflammation research · 2025Review
- Review on effects and mechanisms of plant-derived natural products against breast cancer bone metastasis.Heliyon · 2024Review
- Dry Heating of Curcumin in the Presence of Basic Salts Yields Anti-inflammatory Dimerization Products.ACS omega · 2024Article
- Interrogating Estrogen Signaling Pathways in Human ER-Positive Breast Cancer Cells Forming Bone Metastases in Mice.Endocrinology · 2024Article
- [Curcumin suppresses proliferation, migration and invasion of papillary thyriod cancer B-CPAP cells through the Keap1-Nrf2 pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- Dietary Bioactive Compounds and Breast Cancer.International journal of molecular sciences · 2023Article
- Muscle and Bone Defects in Metastatic Disease.Current osteoporosis reports · 2022Review
- Polyphenols: Bioavailability, Microbiome Interactions and Cellular Effects on Health in Humans and Animals.Pathogens (Basel, Switzerland) · 2022Review
- Curcumin Inhibition of TGFβ signaling in bone metastatic breast cancer cells and the possible role of oxidative metabolites.The Journal of nutritional biochemistry · 2022Article
- Article
- Extracellular Vesicles in Human Milk.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Mediterranean Diet Food Components as Possible Adjuvant Therapies to Counteract Breast and Prostate Cancer Progression to Bone Metastasis.Biomolecules · 2021Review
- Considerations to Be Taken When Carrying Out Medicinal Plant Research-What We Learn from an Insight into the ICPharmaceuticals (Basel, Switzerland) · 2021Review
- A Role for TGFβ Signaling in Preclinical Osteolytic Estrogen Receptor-Positive Breast Cancer Bone Metastases Progression.International journal of molecular sciences · 2021Article
- Annexin A1 is a potential biomarker of bone metastasis in small cell lung cancer.Oncology letters · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Breast cancer (BCa) bone metastases (BMETs) drive osteolysis via a feed-forward loop involving tumoral secretion of osteolytic factors (e.g., PTHrP) induced by bone-matrix-derived growth factors (e.g., TGFβ). In prior experiments, turmeric-derived curcumin inhibited in vivo BMET progression and in vitro TGFβ/Smad-signaling in a TGFβ-stimulated PTHrP-dependent human xenograft BCa BMET model (MDA-SA cells). However, it is unclear whether curcumin or curcumin-glucuronide mediates in vivo protection since curcumin-glucuronide is the primary circulating metabolite in rodents and in humans. Thus, effects of curcumin vs. curcumin-glucuronide on Smad-dependent TGFβ signaling were compared in a series of BCa cell lines forming TGFβ-dependent BMET in murine models, and tissue-specific metabolism of curcumin in mice was examined by LC-MS. While curcumin inhibited TGFβ-receptor-mediated Smad2/3 phosphorylation in all BCa cells studied (human MDA-SA, MDA-1833, MDA-2287 and murine 4T1 cells), curcumin-glucuronide did not. Similarly, curcumin, but not curcumin-glucuronide, blocked TGFβ-stimulated secretion of PTHrP from MDA-SA and 4T1 cells. Because the predominant serum metabolite, curcumin-glucuronide, lacked bioactivity, we examined tissue-specific metabolism of curcumin in mice. Compared to serum and other organs, free curcumin (both absolute and percentage of total) was significantly increased in bone, which was also a rich source of enzymatic deglucuronidation activity. Thus, curcumin, and not curcumin-glucuronide, appears to inhibit bone-tropic BCa cell TGFβ-signaling and to undergo site-specific activation (deconjugation) within the bone microenvironment. These findings suggest that circulating curcumin-glucuronide may act as a prodrug that preferentially targets bone, a process that may contribute to the bone-protective effects of curcumin and other highly glucuronidated dietary polyphenols.
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