Targeting Adiponectin in Breast Cancer

Nehme, Rawan; Diab‐Assaf, Mona; Decombat, Caroline; Delort, Laëtitia; Caldefie-Chézet, Florence

doi:10.3390/biomedicines10112958

Cited by 17 publications

(10 citation statements)

References 146 publications

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“…Our findings showed that Rooibos extract significantly reduced leptin expression in mature adipocytes, once again reflecting its anti-inflammatory properties. Additionally, there is huge interest in adiponectin and its analogs as a potential therapy, not only for all metabolic syndromes but also for several cancer types [ 43 ]. To our knowledge, our team is the first to reveal that Rooibos significantly increases adiponectin expression in 2D and 3D human primary adipocyte cultures, contrary to the published results on 3T3-L1 murine adipocytes, where adiponectin secretion remained unchanged after Rooibos treatment [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Aspalathus linearis (Rooibos) Targets Adipocytes and Obesity-Associated Inflammation

et al. 2023

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Excess weight and obesity are the fifth leading cause of death globally, and sustained efforts from health professionals and researchers are required to mitigate this pandemic-scale problem. Polyphenols and flavonoids found in Aspalathus linearis—a plant widely consumed as Rooibos tea—are increasingly being investigated for their positive effects on various health issues including inflammation. The aim of our study was to examine the effect of Rooibos extract on obesity and the associated low-grade chronic inflammatory state by testing antioxidant activity, cytokine secretions, macrophage polarization and the differentiation of human adipocytes through the development of adipospheroids. Rooibos extract significantly decreased ROS production and the secretion of pro-inflammatory cytokines (IFN-γ, IL-12, IL-2 and IL-17a) in human leukocytes. Additionally, Rooibos extract down-regulated LPS-induced macrophage M1 polarization, shown by a significant decrease in the expression of pro-inflammatory cytokines: TNFα, IL-8, IL-6, IL-1β and CXCL10. In addition, Rooibos inhibited intracellular lipid accumulation and reduced adipogenesis by decreasing the expression of PPARγ, Ap2 and HSL in adipospheroids. A significant decrease in leptin expression was noted and this, more interestingly, was accompanied by a significant increase in adiponectin expression. Using a co-culture system between macrophages and adipocytes, Rooibos extract significantly decreased the expression of all studied pro-inflammatory cytokines and particularly leptin, and increased adiponectin expression. Thus, adding Rooibos tea to the daily diet is likely to prevent the development of obesity associated with chronic low-level inflammation.

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Section: Discussionmentioning

confidence: 99%

Aspalathus linearis (Rooibos) Targets Adipocytes and Obesity-Associated Inflammation

et al. 2023

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“…Adiponectin which ADIPOQ encodes, is secreted by adipocytes and has various biological effects. Several studies suggest that adiponectin has a protective effect against breast cancer [49]. Adiponectin has been shown to induce autophagic cell death in breast cancer through the activation of the AMPK-ULK1 axis regulated by STK11/LKB1 and trigger breast cancer cell death through fatty acid metabolic reprogramming [50,51].…”

Section: Discussionmentioning

confidence: 99%

Single-cell analysis of white adipose tissue reveals the tumor-promoting adipocyte subtypes

Liu

Chen

et al. 2023

Preprint

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Background: The tumor-adipose microenvironment (TAME) is characterized by the enrichment of adipocytes, and is considered a special ecosystem that supports cancer progression. However, the heterogeneity and diversity of adipocytes in TAME remains poorly understood. Methods: We conducted a single-cell RNA-seq analysis of adipocytes in mouse and human white adipose tissue (WAT). We analyzed several adipocyte subtypes to evaluate their relationship and potential as prognostic factors for overall survival (OS). The potential drugs are screened by using bioinformatics methods. The tumor-promoting effects of a typical adipocyte subtype in breast cancer are validated by performing in vitro functional assays and immunohistochemistry (IHC) in clinical samples. Results: We profiled a comprehensive single-cell atlas of adipocyte in mouse and human WAT and described their characteristics, origins, development, functions and interactions with immune cells. Several cancer-associated adipocyte subtypes, namely DPP4+ adipose stem cells in visceral adipose and ADIPOQ+ adipocytes in subcutaneous adipose, are identified. We found that high levels of these subtypes are associated with unfavorable outcomes in four typical adipose-associated cancers. Some potential drugs including Trametinib, Selumetinib and Ulixertinib are discovered. Emphatically, knockdown of adiponectin receptor 1 (AdipoR1) and AdipoR2 impaired the proliferation and invasion of breast cancer cells. Patients with AdipoR2-high breast cancer display significantly shorter relapse-free survival (RFS) than those with AdipoR2-low breast cancer. Conclusion: Our results provide a novel understanding of TAME at the single-cell level. Based on our findings, several adipocyte subtypes have negative impact on prognosis. These cancer-associated adipocytes may serve as key prognostic predictor and potential targets for treatment in the future.

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“…This concept is now re-emerging (discussed in [146]), due to the implementation of drug repurposing (Denosumab, Metformin, Letrozole, see Suppl. Table ) as well as principally new approaches like adiponectin receptor targeting molecules [147].…”

Section: Future Perspectives and Conclusionmentioning

confidence: 99%

BRCA Mutations: The Achilles Heel of Breast, Ovarian and Other Epithelial Cancers

Loboda¹,

Adonin²,

Zvereva³

et al. 2023

Preprint

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Two related tumor suppressor genes, Brca1 and Brca2, attract a lot of attention from both fundamental and clinical points of view. Oncogenic hereditary mutations in these genes are firmly linked to the early onset of breast and ovarian cancers. However, the molecular mechanisms that drive extensive mutagenesis in these genes are not known. In this review we hypothesize that one of the potential mechanisms behind this phenomenon can be mediated by Alu mobile genomic elements. Linking mutations in the BRCA1 and BRCA2 genes to the general mechanism(s) of genome stability and DNA repair is critical to ensure the rationalized choice of anti-cancer therapy. Accordingly, we review the literature available on mechanisms of DNA damage repair where these proteins are involved in and how the inactivating mutations in these genes (BRCAness) can be exploited in anti-cancer therapy. We also propose a hypothesis that explains why breast and ovarian epithelial tissues are preferentially susceptible to mutations in BRCA genes. Finally, we discuss perspectives of novel therapeutic approaches for treating BRCAness cancers.

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Targeting Adiponectin in Breast Cancer

Cited by 17 publications

References 146 publications

Aspalathus linearis (Rooibos) Targets Adipocytes and Obesity-Associated Inflammation

Aspalathus linearis (Rooibos) Targets Adipocytes and Obesity-Associated Inflammation

Single-cell analysis of white adipose tissue reveals the tumor-promoting adipocyte subtypes

BRCA Mutations: The Achilles Heel of Breast, Ovarian and Other Epithelial Cancers

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