Hydroxytyrosol Inhibits MDSCs and Promotes M1 Macrophages in Mice With Orthotopic Pancreatic Tumor

Wang, Botao; Yang, Lei; Li, Tianyu; Xun, Jing; Zhuo, Yong; Zhang, Lanqiu; Zhang, Qi; Wang, Ximo

doi:10.3389/fphar.2021.759172

Cited by 4 publications

(4 citation statements)

References 43 publications

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“…[ 51 ] The proposed drug delivery system could effectively optimize the distribution of the inhibitor, which is the premise of successful immunotherapy, since p ‐STAT3 is the key pivot in modulating the immunosuppression microenvironment in pancreatic cancer therapy. [ 52 ]…”

Section: Resultsmentioning

confidence: 99%

Penetrating Micelle for Reversing Immunosuppression and Drug Resistance in Pancreatic Cancer Treatment

Chen

Wang

et al. 2022

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Pancreatic ductal adenocarcinoma (PDAC) is on of the most lethal malignant tumors with relatively poor prognosis, characterized with insufficient drug penetration, low immune response and obvious drug resistances. The therapeutic inefficiency is multifactorially related to its specific tumor microenvironment (TME), which is representatively featured as rich stroma and immunosuppression. In this work, a versatile drug delivery system is developed that can coencapsulate two prodrugs modified from gemcitabine (GEM) and a signal transducer and activator of transcription 3 (STAT3) inhibitor (HJC0152), and the gradient pH variation is further sensed in the TME of PDAC to achieve a higher penetration by reversing its surficial charges. The escorted prodrugs can release GEM intracellularly, and respond to the hypoxic condition to yield the parental STAT3 inhibitor HJC0152, respectively. By inhibiting STAT3, the tumor immunosuppression microenvironment can be re‐educated through the reversion of M2‐like tumor associated macrophages (M2‐TAMs), recruitment of cytotoxic T lymphocytes and downregulation of regulatory T cells (Tregs). Furthermore, cytidine deaminase (CDA) and α‐smooth muscle actin (α‐SMA) expression can be downregulated, plus the lipid modification of GEM, the drug resistance of GEM can be greatly relieved. Based on the above design, a synergetic therapeutic efficacy in PDAC treatment can be achieved to provide more opportunity for clinical applications.

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Section: Resultsmentioning

confidence: 99%

Penetrating Micelle for Reversing Immunosuppression and Drug Resistance in Pancreatic Cancer Treatment

Chen

Wang

et al. 2022

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“…In fact, the compound inhibited the proliferation of tumour cells, was able to activate the signal transducers and activators of the transcription 3 (STAT 3)/CCND1 signalling pathway, increased the proportion of M1 macrophages, and enhanced the anti-cancer effects of the anti-CD 47 antibody. Additionally, the combination of HT with plumbagin (PLB) resulted in more cell death compared with HT or PLB alone [ 96 ].…”

Section: Potential Effects Of Oleuropein and Hydroxytyrosol On Neurob...mentioning

confidence: 99%

Olive Oil Components as Novel Antioxidants in Neuroblastoma Treatment: Exploring the Therapeutic Potential of Oleuropein and Hydroxytyrosol

Gonçalves,

Aiello,

Rodríguez-Pérez

et al. 2024

Nutrients

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In this review, we explored the therapeutic potential of oleuropein (OLE) and hydroxytyrosol (HT) in the treatment of neuroblastoma (NB). NB is an extracranial tumour that predominantly affects children aged between 17 and 18 months. Recurrence and drug resistance have emerged as the biggest challenges when treating NB, leading to a crucial need for new therapeutic approaches. Food of the Mediterranean Diet (MD) presents several health benefits, including that of cancer treatment. In this review, we emphasised olive oil since it is one of the main liquid ingredients of the MD. OLE is the principal phenolic compound that constitutes olive oil and is hydrolysed to produce HT. Considering that tumour cells produce increased amounts of reactive oxygen species, this review highlights the antioxidant properties of OLE and HT and how they could result in increased cellular antioxidant defences and reduced oxidative damage in NB cells. Moreover, we highlight that these phenolic compounds lead to apoptosis and cell cycle arrest, reduce the side effects caused by conventional treatments, and activate tumours that become dormant as a resistance mechanism. Future research should explore the effects of these compounds and other antioxidants on the treatment of NB in vivo.

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“…In an in vivo orthotopic model of pancreatic cancer, obtained by injecting mouse pancreatic cancer cells Panc02 in C57BL/6 mice, proved that 200 mg/kg HT for 10 days suppressed tumor growth and proliferation. These results seem to depend on the modulation of the tumor microenvironment, since HT was able to reduce the accumulation of myeloid-derived suppressor cells in lymphoid organs, bone marrow, and tumor tissues [ 81 ].…”

Section: Effects Of Ole and Ht On Solid Tumorsmentioning

confidence: 99%

“…Treatment of mouse pancreatic cancer cell line Panc02 with 50 μM, 150 μM, and 200 μM HT for 48 h elicited a dose-dependent inhibition of cell proliferation and induction of apoptosis. Further experimental evidence revealed that 100 μM HT inhibited the expression of phospho-STAT3 and Cyclin D1 after 24 h [ 81 ].…”

Section: Effects Of Ole and Ht On Solid Tumorsmentioning

confidence: 99%

Use of Oleuropein and Hydroxytyrosol for Cancer Prevention and Treatment: Considerations about How Bioavailability and Metabolism Impact Their Adoption in Clinical Routine

Gervasi,

Pojero

2024

Biomedicines

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The fact that the Mediterranean diet could represent a source of natural compounds with cancer-preventive and therapeutic activity has been the object of great interest, especially with regard to the mechanisms of action of polyphenols found in olive oil and olive leaves. Secoiridoid oleuropein (OLE) and its derivative hydroxytyrosol (3,4-dihydroxyphenylethanol, HT) have demonstrated anti-proliferative properties against a variety of tumors and hematological malignancies both in vivo and in vitro, with measurable effects on cellular redox status, metabolism, and transcriptional activity. With this review, we aim to summarize the most up-to-date information on the potential use of OLE and HT for cancer treatment, making important considerations about OLE and HT bioavailability, OLE- and HT-mediated effects on drug metabolism, and OLE and HT dual activity as both pro- and antioxidants, likely hampering their use in clinical routine. Also, we focus on the details available on the effects of nutritionally relevant concentrations of OLE and HT on cell viability, redox homeostasis, and inflammation in order to evaluate if both compounds could be considered cancer-preventive agents or new potential chemotherapy drugs whenever their only source is represented by diet.

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Hydroxytyrosol Inhibits MDSCs and Promotes M1 Macrophages in Mice With Orthotopic Pancreatic Tumor

Cited by 4 publications

References 43 publications

Penetrating Micelle for Reversing Immunosuppression and Drug Resistance in Pancreatic Cancer Treatment

Penetrating Micelle for Reversing Immunosuppression and Drug Resistance in Pancreatic Cancer Treatment

Olive Oil Components as Novel Antioxidants in Neuroblastoma Treatment: Exploring the Therapeutic Potential of Oleuropein and Hydroxytyrosol

Use of Oleuropein and Hydroxytyrosol for Cancer Prevention and Treatment: Considerations about How Bioavailability and Metabolism Impact Their Adoption in Clinical Routine

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