Oleuropein is a natural inhibitor of PAI-1-mediated proliferation in human ER-/PR- breast cancer cells

Tzekaki, Elena E.; Geromichalos, George D.; Lavrentiadou, Sophia; Tsantarliotou, Maria; Pantazaki, Αnastasia A.; Papaspyropoulos, Angelos

doi:10.1007/s10549-020-06054-x

Cited by 27 publications

(17 citation statements)

References 57 publications

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“…Researchers (Bayat et al, 2019;Lu et al, 2021) found that oleuropein reduced the expression of HDAC2, HDAC3, and HDAC4, caused apoptosis, and delayed cellular migration and invasion in a dose-dependent manner. Lu et al (2019) showed that oleuropein treatment significantly inhibited hepatocyte growth factor, or Tzekaki et al identified oleuropein as a natural plasminogen activator inhibitor-1 (PAI-1) inhibitor through incrementally destabilizing PAI-1 levels selectively in ER-/PR-breast cancer cells, accompanied by downstream caspase activation and cell growth inhibition, which suggested that oleuropein-mediated PAI-1 destabilization may confer clinical benefit in TNBCr (Tzekaki et al, 2021).…”

Section: Breast Cancermentioning

confidence: 99%

An updated review on the potential antineoplastic actions of oleuropein

Zheng

Liu

Xiao

et al. 2021

Phytotherapy Research

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It is a phenolic compound and the most luxuriant in olives. The detailed information related to the anticancer effects of oleuropein was collected from the internet database PubMed/Medline, ResearchGate, Web of Science, Wiley Online Library, and Cnki using appropriate keywords until the end of October 2021. Oleuropein has been shown to have antioxidant, anticancer, antiinflammatory, cardioprotective, neuroprotective, and hepatoprotective effects. Previous studies also revealed that oleuropein could effectively inhibit the malignant progression of esophageal cancer, gastric cancer, breast cancer, lung cancer, liver cancer, pancreatic cancer, ovarian cancer, prostate cancer, and cervical cancer. Recently, the role of oleuropein in inhibiting tumor cell proliferation, invasion, and migration and inducing tumor cell apoptosis has gained extensive attention. In this review, we have summarized the latest research progress related to the antioncogenic mechanisms and the potential role of oleuropein in targeting different human malignancies. Based on these findings, it can be concluded that oleuropein can function as a promising chemopreventive and chemotherapeutic agent against cancer, but its more detailed anticancer effects and underlying mechanisms need to be further validated in future preclinical as well as clinical studies.

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Section: Breast Cancermentioning

confidence: 99%

An updated review on the potential antineoplastic actions of oleuropein

Zheng

Liu

Xiao

et al. 2021

Phytotherapy Research

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“…Of note, potentially harmful senescent cells can be selectively targeted and eliminated by a class of compounds collectively referred to as senolytics [ 152 , 153 ]. It remains to be explored whether natural anti-cancer or anti-oxidative compounds [ 154 , 155 ] may additionally act as senolytic agents.…”

Section: Discussionmentioning

confidence: 99%

Interplay of Developmental Hippo–Notch Signaling Pathways with the DNA Damage Response in Prostate Cancer

Mourkioti

Angelopoulou

Belogiannis

et al. 2022

Cells

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Prostate cancer belongs in the class of hormone-dependent cancers, representing a major cause of cancer incidence in men worldwide. Since upon disease onset almost all prostate cancers are androgen-dependent and require active androgen receptor (AR) signaling for their survival, the primary treatment approach has for decades relied on inhibition of the AR pathway via androgen deprivation therapy (ADT). However, following this line of treatment, cancer cell pools often become resistant to therapy, contributing to disease progression towards the significantly more aggressive castration-resistant prostate cancer (CRPC) form, characterized by poor prognosis. It is, therefore, of critical importance to elucidate the molecular mechanisms and signaling pathways underlying the progression of early-stage prostate cancer towards CRPC. In this review, we aim to shed light on the role of major signaling pathways including the DNA damage response (DDR) and the developmental Hippo and Notch pathways in prostate tumorigenesis. We recapitulate key evidence demonstrating the crosstalk of those pathways as well as with pivotal prostate cancer-related ‘hubs’ such as AR signaling, and evaluate the clinical impact of those interactions. Moreover, we attempt to identify molecules of the complex DDR–Hippo–Notch interplay comprising potentially novel therapeutic targets in the battle against prostate tumorigenesis.

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“…Immunoblotting from immunoprecipitates and cell lysates was carried out as previously described (Pefani et al , 2014; Tzekaki et al , 2021a,b). The following primary antibodies were used at a concentration of 1:1,000; β‐CATENIN (sc‐7199), p73 (ep436Y), YAP (sc‐15404 and sc‐101199), HES1 (AB5702), GAPDH (Abcam;2251‐1; 1/10,000), TAZ (sc‐48805 and Ab118373), FLAG (M2; Agilent; 200472‐21), RASSF1A (sc‐58470), NANOG (Cell Signaling; 4893S), OCT4 (ab19857), SOX2 (MAB4423; 1/500), LAMIN B1 (Ab16048; 1/10,000), RNF4 (Novus Biologicals), TEAD1 (BD Transduction Laboratories; 610922), p73 (EP436Y; ½,000), Ub (Cell Signaling; 3936), HA (Cell Signaling; 3724S), ICN1 (Cell Signaling; 4147S), β‐ACTIN (Cell Signaling; 4967L), and HRP‐conjugated anti‐mouse and anti‐rabbit secondary antibodies were used at a concentration of 1:5,000 (Jackson Immunoresearch).…”

Section: Methodsmentioning

confidence: 99%

RASSF1A disrupts the NOTCH signaling axis via SNURF/RNF4‐mediated ubiquitination of HES1

et al. 2021

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RASSF1A promoter methylation has been correlated with tumor dedifferentiation and aggressive oncogenic behavior. Nevertheless, the underlying mechanism of RASSF1A‐dependent tumor dedifferentiation remains elusive. Here, we show that RASSF1A directly uncouples the NOTCH‐HES1 axis, a key suppressor of differentiation. Interestingly, the crosstalk of RASSF1A with HES1 occurs independently from the signaling route connecting RASSF1A with the Hippo pathway. At the molecular level, we demonstrate that RASSF1A acts as a scaffold essential for the SUMO‐targeted E3 ligase SNURF/RNF4 to target HES1 for degradation. The reciprocal relationship between RASSF1A and HES1 is evident across a wide range of human tumors, highlighting the clinical significance of the identified pathway. We show that HES1 upregulation in a RASSF1A‐depleted environment renders cells non‐responsive to the downstream effects of γ‐secretase inhibitors (GSIs) which restrict signaling at the level of the NOTCH receptor. Taken together, we report a mechanism through which RASSF1A exerts autonomous regulation of the critical Notch effector HES1, thus classifying RASSF1A expression as an integral determinant of the clinical effectiveness of Notch inhibitors.

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Oleuropein is a natural inhibitor of PAI-1-mediated proliferation in human ER-/PR- breast cancer cells

Cited by 27 publications

References 57 publications

An updated review on the potential antineoplastic actions of oleuropein

An updated review on the potential antineoplastic actions of oleuropein

Interplay of Developmental Hippo–Notch Signaling Pathways with the DNA Damage Response in Prostate Cancer

RASSF1A disrupts the NOTCH signaling axis via SNURF/RNF4‐mediated ubiquitination of HES1

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