Datasets:
Tasks:
Token Classification
Modalities:
Text
Formats:
parquet
Sub-tasks:
named-entity-recognition
Languages:
English
Size:
1K - 10K
License:
PMCID
stringclasses 6
values | Sentences
stringlengths 22
960
| entities
listlengths 0
9
|
|---|---|---|
PMC10968586
|
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.
|
[] |
PMC10968586
|
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.
|
[] |
PMC10968586
|
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.
|
[] |
PMC10968586
|
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.
|
[] |
PMC10968586
|
Cancer insurgence and progression are complex processes, depending on the combination of unmodifiable genetic and modifiable environmental/lifestyle-related factors.
|
[] |
PMC10968586
|
With this premise, it sounds perfectly understandable that scientific evidence has corroborated the role of a healthy diet and dietary intervention as potentially beneficial approaches contributing to cancer prevention .
|
[] |
PMC10968586
|
Epidemiological and experimental evidence has confirmed that the so-called Mediterranean diet is a source of molecules that may mitigate cancer risk factors like chronic inflammation and redox imbalance, thus participating in the prevention of carcinogenesis in terms of loss of cell cycle regulation and proper immune modulation, as well as in the inhibition of angiogenesis and metastasis.
|
[] |
PMC10968586
|
Moreover, some of these natural compounds may have a cytotoxic effect, making them interesting alternatives to or candidates for integration into conventional therapeutic approaches .
|
[] |
PMC10968586
|
Among Mediterranean diet phenols, secoiridoid oleuropein (OLE) is the most abundant phenolic compound in Olea europaea L. tree leaves (OLE content up to 14–19% in olive leaves), followed by its degradation derivative hydroxytyrosol (3,4-dihydroxyphenylethanol, HT, 2.28 mg/g of olive leaf extract) (Figure 1) .
|
[] |
PMC10968586
|
OLE and HT are also found in the fruit of Olea europaea L. and in olive oil; thus, they are easily ingested as part of a routine diet, but they can also be obtained from other sources, e.g., olive mill wastewater .
|
[] |
PMC10968586
|
Both compounds have attracted attention for their accessibility, safe profile, powerful antioxidant and scavenging activity against reactive oxygen species (ROS), and controversial anti-inflammatory action.
|
[] |
PMC10968586
|
For more than two decades, OLE and HT (together or alone) have been the focus of intense research efforts in the context of infectious diseases and prevention/management of chronic non-communicable diseases, including cancer, with encouraging results from in vitro and in vivo models .
|
[] |
PMC10968586
|
On this basis, it would be difficult to understand the reasons behind the lack of systematic testing of OLE and HT as supplements to prevent the insurgence of cancer or support the management of hematological malignancies and solid tumors.
|
[] |
PMC10968586
|
This becomes clearer considering that, despite promising proof in the field, experimental evidence about OLE and HT bioavailability in humans and animals clearly demonstrates that OLE and HT act as cancer-preventive agents and cytotoxic drugs mainly at concentrations far from plasma levels reachable through nutrition, an aspect often interpreted as marginal that we discuss in detail in this review.
|
[] |
PMC10968586
|
Also, as explained in the following paragraphs, the complexity and diversity of molecular mechanisms resulting in net OLE and HT action has led to questions regarding the possibility that these compounds might even facilitate the expansion of neoplastic clones at nutritionally relevant concentrations.
|
[] |
PMC10968586
|
In this review, we discuss the available data on the use of OLE and HT as anti-cancer drugs and the feasibility of their application in the context of clinical routine now or in the near future.
|
[] |
PMC10968586
|
OLE and HT activity against solid tumor insurgence and development has been challenged in a large number of experimental models, both in vivo and in vitro.
|
[] |
PMC10968586
|
No single shared molecular mechanism and/or triggered cellular response seems implicated in OLE and HT cytotoxicity, resulting in an articulated frame that imposes a separate dissertation for every type of studied solid tumor.
|
[] |
PMC10968586
|
To facilitate critical interpretation, in each subsection, OLE and HT assayed doses are indicated, with the half-maximal inhibitory concentration (IC50) and the half-maximal effective concentration (EC50) reported as exact values, mean ± standard deviation (S.D.), or mean ± standard error of the mean (S.E.M.) whenever provided by the authors.
|
[] |
PMC10968586
|
A list of experimental models used to study OLE and HT cytotoxicity in cancer cells is reported in Table 1.
|
[] |
PMC10968586
|
Malignant melanoma is a malignancy arising from the transformation of melanocytes, with increasing incidence worldwide.
|
[] |
PMC10968586
|
On the basis of the tissue where the primary lesion appears, four major subtypes can be distinguished: cutaneous melanoma (non-glabrous skin), acral melanoma (glabrous skin), mucosal melanoma (melanocytes in the mucosal tissues), and uveal melanoma (uveal tract of the eye).
|
[] |
PMC10968586
|
Among these major subtypes, it is possible to distinguish some particular variants: amelanotic/hypomelanotic melanoma, a subtype of cutaneous melanoma with low or absent melanin; desmoplastic melanoma, a spindle cell tumor exhibiting signs of dense scar-like fibrosis; spitzoid melanoma, sharing histopathological characteristics with Spitz nevi; acral lentiginous melanoma, with a lentiginous growth pattern .
|
[] |
PMC10968586
|
OLE seems to be effective in the prevention of skin carcinogenesis in vivo.
|
[] |
PMC10968586
|
Orally administered 10 mg/kg and 25 mg/kg OLE reduced skin carcinogenesis (expressed in terms of number of tumors per mouse) in UVB-irradiated albino hairless HOS: HR-1 mice .
|
[
{
"end": 162,
"label": "CellLine",
"start": 159,
"text": "HOS"
},
{
"end": 168,
"label": "CellLine",
"start": 164,
"text": "HR-1"
}
] |
PMC10968586
|
For 25 mg/kg OLE, this effect was associated with a persistent reduction in (I) the total volume of tumors per mouse, (II) the expression levels of invasion enzymes matrix metalloproteinase 2 (MMP2), pro-MMP9, and MMP9, (III) tissue angiogenesis marker vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) levels, and (IV) the percentage of skin Ki-67+ cells and platelet endothelial cell adhesion molecule-1 (PECAM-1 or CD31)+ areas .
|
[] |
PMC10968586
|
OLE also seems effective in the prevention of melanoma growth and metastasis.
|
[] |
PMC10968586
|
In an in vivo B16F10 (mouse melanoma cell line) allograft model of high-fat diet (HFD)-induced melanoma progression in C57BL/6N mice, HFD containing 0.02% and 0.04% OLE reduced HFD-driven tumor growth and lymph node metastasis, with a mechanism involving (I) inhibition of cell proliferation, as indicated by the reduction in the percentage of cells positive for proliferation markers Ki67, Cyclin D1, and cyclin-dependent kinase 4 (CDK4) cells, (II) suppression of angiogenesis (reduction in CD31, VE-cadherin expression, VEGF-A, VEGF-C, VEGF-D, VEGF receptor 2 -VEGFR2- and VEGFR3), and (III) inhibition of lymphangiogenesis, as proved by staining for lymphatic vessel endothelial hyaluronan receptor (LYVE-1).
|
[
{
"end": 20,
"label": "CellLine",
"start": 14,
"text": "B16F10"
},
{
"end": 127,
"label": "CellLine",
"start": 119,
"text": "C57BL/6N"
}
] |
PMC10968586
|
According to further in vitro experimental assays, OLE anti-angiogenetic and lymphangiogenetic action relies on the inhibition of lipid and M2-macrophage accumulation .
|
[] |
PMC10968586
|
In vitro results for OLE are conflicting.
|
[] |
PMC10968586
|
Incubation of human amelanotic melanoma cell line C32 with 100 μM, 400 μM, and 1000 μM OLE for 72 h promoted cell viability .
|
[
{
"end": 53,
"label": "CellLine",
"start": 50,
"text": "C32"
}
] |
PMC10968586
|
On the contrary, incubation of human melanoma cell lines A375, WM266-4, and M21 with 250 μM, 500 μM, and 800 μM OLE for 72 h produced a dose-dependent decrease in cell viability.
|
[
{
"end": 61,
"label": "CellLine",
"start": 57,
"text": "A375"
},
{
"end": 70,
"label": "CellLine",
"start": 63,
"text": "WM266-4"
},
{
"end": 79,
"label": "CellLine",
"start": 76,
"text": "M21"
}
] |
PMC10968586
|
As deepened in A375 cells, an increase in OLE effectiveness with time may be detected.
|
[
{
"end": 19,
"label": "CellLine",
"start": 15,
"text": "A375"
}
] |
PMC10968586
|
OLE induced inhibition of cell viability after 24 h at a concentration of 800 μM, whereas after 48 and 72 h, a decrease in the percentage of viable cells became significant with a concentration as low as 250 μM .
|
[] |
PMC10968586
|
After 48 h treatment, 500 μM OLE increased the rate of apoptosis in A375 cells.
|
[
{
"end": 72,
"label": "CellLine",
"start": 68,
"text": "A375"
}
] |
PMC10968586
|
In addition, 24 h incubation with 250 μM OLE was sufficient to reduce invasiveness of A375 cells, while 48 h incubation with the same OLE concentration reduced the phosphorylation of pro-survival kinase Akt .
|
[
{
"end": 90,
"label": "CellLine",
"start": 86,
"text": "A375"
}
] |
PMC10968586
|
As regards in vitro evidence for HT, the effects on cell growth seem to be cell line-dependent.
|
[] |
PMC10968586
|
Treatment of C32 cells with 100 μM HT for 72 h increased cell viability, which was instead reduced by incubation with 400 μM and 1000 μM HT .
|
[
{
"end": 16,
"label": "CellLine",
"start": 13,
"text": "C32"
}
] |
PMC10968586
|
Incubation of human melanoma cell line A375 with 100 μM and 200 μM HT significantly diminished cell viability after 48 h. On the contrary, 48 h treatment of melanoma cell line MNT1 with 100 μM and 200 μM HT had no significant effect on cell viability.
|
[
{
"end": 43,
"label": "CellLine",
"start": 39,
"text": "A375"
},
{
"end": 180,
"label": "CellLine",
"start": 176,
"text": "MNT1"
}
] |
PMC10968586
|
The authors attributed this dissimilarity between the mentioned cell lines to differences in the active metabolic pathways.
|
[] |
PMC10968586
|
Expression analysis revealed a significant transcriptional upregulation of lactate dehydrogenase B (LDHB) and LDHC (accounting for lactate conversion into pyruvate) and glutamine synthetase (GLUL) in MNT1 cells in comparison with the A375 cell line, while sodium-coupled neutral amino acid transporter 1 (SNAT1) and SNAT2 (involved in glutamine transport within the cell), monocarboxylate transporter 4 (MCT4, accounting for lactate export), glycolytic enzyme glucose-6-phosphate dehydrogenase (G6PD), and excitatory amino acid transporter 3 (EEAT3) were downregulated in MNT1 cells vs. A375 .
|
[
{
"end": 204,
"label": "CellLine",
"start": 200,
"text": "MNT1"
},
{
"end": 238,
"label": "CellLine",
"start": 234,
"text": "A375"
},
{
"end": 576,
"label": "CellLine",
"start": 572,
"text": "MNT1"
},
{
"end": 591,
"label": "CellLine",
"start": 587,
"text": "A375"
}
] |
PMC10968586
|
In a further report, treatment of human melanoma cell lines A375, HT-144, and M74 with 50–250 μM HT produced a dose- and time-dependent decrease in cell viability after 24, 48, and 72 h .
|
[
{
"end": 64,
"label": "CellLine",
"start": 60,
"text": "A375"
},
{
"end": 72,
"label": "CellLine",
"start": 66,
"text": "HT-144"
},
{
"end": 81,
"label": "CellLine",
"start": 78,
"text": "M74"
}
] |
PMC10968586
|
A detailed analysis on A375 cells (treated with 250 μM, 375 μM, and 500 μM HT) and HT-144 cells (incubated with 250 μM, 350 μM, and 450 μM HT) performed for 24 and 48 h revealed an increase in the rate of apoptosis in both cell lines, with a dose- and time-dependent increase in tumor suppressor p53 and reduction in growth-promoting kinase Akt protein levels .
|
[
{
"end": 27,
"label": "CellLine",
"start": 23,
"text": "A375"
},
{
"end": 89,
"label": "CellLine",
"start": 83,
"text": "HT-144"
}
] |
PMC10968586
|
The activation of apoptosis pathway was further confirmed by an increase in apoptosis markers pro-activated and cleaved (activated) forms of caspase-3, a dose- and time-dependent increase in cleavage (activation) of poly ADP-ribose polymerase 1 (PARP-1), and a dose-dependent increase in the phosphorylation of histone H2AX (γH2AX) .
|
[] |
PMC10968586
|
HT-mediated induction of apoptosis was related to ROS accumulation in both cell lines at the indicated HT concentrations, which was detected after 24 and 48 h .
|
[] |
PMC10968586
|
Thyroid cancer is a category of neoplastic lesions with a highly variable degree of aggressiveness, arising from parafollicular C cells (resulting in medullary thyroid cancers) and follicular thyroid cells (producing follicular thyroid cancer, papillary thyroid cancer, poorly differentiated thyroid cancer, Hürthle cell cancers, and anaplastic thyroid cancer) .
|
[] |
PMC10968586
|
In vitro, treatment of human papillary thyroid carcinoma cell line TPC-1 and poorly differentiated thyroid gland carcinoma cell line BCPAP with 50–100 μM OLE for 48 h produced a significant reduction in cell viability attributable to S phase and G2/M phase cell cycle block, respectively.
|
[
{
"end": 72,
"label": "CellLine",
"start": 67,
"text": "TPC-1"
},
{
"end": 138,
"label": "CellLine",
"start": 133,
"text": "BCPAP"
}
] |
PMC10968586
|
In both cell lines, 50–100 μM OLE exerted an antioxidant activity against hydrogen peroxide (H2O2)-induced perturbation of ROS homeostasis.
|
[] |
PMC10968586
|
Also, 100 μM OLE caused a short-lasting (30 to 60 min) reduction in phosphorylated forms pro-survival kinases ERK (phospho-ERK) and Akt (phospho-Akt) in TPC-1 and BCPAP cells .
|
[
{
"end": 158,
"label": "CellLine",
"start": 153,
"text": "TPC-1"
},
{
"end": 168,
"label": "CellLine",
"start": 163,
"text": "BCPAP"
}
] |
PMC10968586
|
Incubation of papillary thyroid cancer cell lines TPC-1 and FB-2 with 324–973 μM HT decreased cell viability after 24 and 48 h in a dose-dependent manner.
|
[
{
"end": 55,
"label": "CellLine",
"start": 50,
"text": "TPC-1"
},
{
"end": 64,
"label": "CellLine",
"start": 60,
"text": "FB-2"
}
] |
PMC10968586
|
A stronger action was exerted on follicular thyroid cancer cell line WRO, whose cell viability was reduced even at lower doses of HT after 24 h (162 μM) and 48 h (65 μM) treatment .
|
[
{
"end": 72,
"label": "CellLine",
"start": 69,
"text": "WRO"
}
] |
PMC10968586
|
After 24 h incubation, 324 μM HT elicited an increase in the percentage of apoptotic and necrotic cells in all the three mentioned cell lines (with a concomitant downregulation of pro-proliferative cyclin D1 and upregulation of tumor suppressor p21 at both mRNA and protein levels), increased protein level of tumor suppressor p53, and activated the intrinsic pathway of apoptosis, as corroborated by the increase in cleaved PARP and cleaved caspase-3 levels, Bcl-2-associated agonist of cell death (Bad) and caspase-9 protein levels, and the release of mitochondrial cytochrome c .
|
[] |
PMC10968586
|
Currently, lung cancer represents the most commonly diagnosed cancer and the main cause of cancer-related deaths worldwide, including small cell carcinoma and more common non-small cell carcinoma .
|
[] |
PMC10968586
|
In adenocarcinomic human alveolar epithelial cells A549 (a model for non-small cell lung cancer), 50 μM and 150 μM OLE-induced apoptosis after 24 h incubation was mediated by the decrement in Bcl-2 and Bcl-XL anti-apoptotic proteins flanked by the increase in (I) mitochondrial-located pro-apoptotic protein Bax, (II) cytochrome c release from the mitochondria, (III) activation of apoptosome component apoptotic protease activating factor-1 (Apaf-1), (IV) activation of caspase-3, and (V) mitochondrial methylglyoxal detoxicating enzyme Glo2 (mGlo2), which physically interacted with Bax .
|
[
{
"end": 55,
"label": "CellLine",
"start": 51,
"text": "A549"
}
] |
PMC10968586
|
Consistent with these data, incubation of non-small cell lung cancer cell line H1299 with 50–200 μM OLE for 24 h elicited a dose-dependent G2/M phase cell cycle block and apoptosis, with effects on Bcl-2, Bax, cytochrome c, and caspase-3 that were similar to those documented for A549 cells .
|
[
{
"end": 84,
"label": "CellLine",
"start": 79,
"text": "H1299"
},
{
"end": 284,
"label": "CellLine",
"start": 280,
"text": "A549"
}
] |
PMC10968586
|
However, the underlying molecular mechanism ruling OLE activity differed between the two cell lines.
|
[] |
PMC10968586
|
The effects elicited by 150 μM OLE on mGlo2 levels in A549 cells were strictly dependent on OLE-induced increase in superoxide dismutase 2 (SOD2) detoxicating action against superoxide (O2), and on the inhibition of the Akt signalling pathway.
|
[
{
"end": 58,
"label": "CellLine",
"start": 54,
"text": "A549"
}
] |
PMC10968586
|
This was not surprising, since in A549 cells, O2 supports Akt activations, promoting cell survival .
|
[
{
"end": 38,
"label": "CellLine",
"start": 34,
"text": "A549"
}
] |
PMC10968586
|
In H1299 cells, the observed apoptosis was instead determined by OLE-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK), accompanied by an increased rate of phosphorylation of activating transcription factor-2 (ATF-2), involved in cell cycle regulation, as documented in both tumorigenesis and cell death, and the upregulation of genes ruling cell metabolism and apoptosis .
|
[
{
"end": 8,
"label": "CellLine",
"start": 3,
"text": "H1299"
}
] |
PMC10968586
|
In A549 cell line, HT showed an increase in effectiveness of its anti-proliferative activity with respect to time, with the IC50 values changing from 230.60 μM to 149.36 μM in 72 h .
|
[
{
"end": 7,
"label": "CellLine",
"start": 3,
"text": "A549"
}
] |
PMC10968586
|
This piece of data was confirmed in another report.
|
[] |
PMC10968586
|
In fact, for A549 cells, mean IC50 ± S.E.M. = 147.0 ± 16.5 μM was reported after 48 h incubation .
|
[
{
"end": 17,
"label": "CellLine",
"start": 13,
"text": "A549"
}
] |
PMC10968586
|
Malignant pleural mesothelioma arises from mesothelial cells and is characterized by a pronounced aggressiveness and poor prognosis.
|
[] |
PMC10968586
|
On the basis of histological features, mesothelioma is classified as epithelioid, sarcomatoid, or biphasic, with epithelioid type offering the best median survival .
|
[] |
PMC10968586
|
Pleural epithelioid mesothelioma REN cell line was utilized to demonstrate that OLE exhibited a cytotoxic activity (IC50 = 25 μg/mL, ≈46 μM), and that both OLE and HT (10–100 μM) mobilized extracellular Ca in a dose-dependent manner .
|
[
{
"end": 36,
"label": "CellLine",
"start": 33,
"text": "REN"
}
] |
PMC10968586
|
Breast cancer is the most frequent malignant tumor in women worldwide, with a constantly rising incidence .
|
[] |
PMC10968586
|
Treatment of breast cancer is based on the molecular subtype, a classification that in the first instance takes into account the immunohistochemically assayed expression of hormone receptors estrogen receptor (ER) and progesterone receptor (PR), and gene amplification or overexpression of human epidermal growth factor receptor 2 (HER2).
|
[] |
PMC10968586
|
Triple negative breast cancer identifies a category of tumors lacking the three mentioned receptors .
|
[] |
PMC10968586
|
In an in vivo model of tumor xenograft (triple negative MDA-MB-231 cell line) in BALB/c OlaHsd-foxn1 mice, animals receiving 50 mg/kg OLE for 4 weeks showed a decrease in tumor size, together with a reduction in actors involved in cell growth/proliferation: transcription factor NF-κB and cyclin D1 .
|
[
{
"end": 66,
"label": "CellLine",
"start": 56,
"text": "MDA-MB-231"
},
{
"end": 87,
"label": "CellLine",
"start": 81,
"text": "BALB/c"
}
] |
PMC10968586
|
Instead, levels of tumor suppressor p21 increased after OLE injection.
|
[] |
PMC10968586
|
The effects elicited by OLE were accompanied by the induction of apoptosis, as demonstrated by caspase-3 activation, increase in Bax levels, and reduction in Bcl-2 protein expression .
|
[] |
PMC10968586
|
In vitro, OLE action appears to be independent of HER2 gene amplification/overexpression and hormone receptor status.
|
[] |
PMC10968586
|
Using MCF-7 cell line, which is devoid of HER-2 overexpression , 200 μg/mL (≈370 μM) OLE for 48 h showed a specific cytotoxic effect on MCF-7 cell line, leaving the non-cancerous cell line MCF-10A unharmed.
|
[
{
"end": 11,
"label": "CellLine",
"start": 6,
"text": "MCF-7"
},
{
"end": 141,
"label": "CellLine",
"start": 136,
"text": "MCF-7"
},
{
"end": 196,
"label": "CellLine",
"start": 189,
"text": "MCF-10A"
}
] |
PMC10968586
|
The observed effect on cell viability was accompanied by the upregulation of the expression of Prdx1-Prdx6, encoding for antioxidant and chaperone proteins peredoxins .
|
[] |
PMC10968586
|
The induction of apoptosis triggered by the same concentration of OLE in MCF-7 cells was confirmed in another study after 12 h incubation .
|
[
{
"end": 78,
"label": "CellLine",
"start": 73,
"text": "MCF-7"
}
] |
PMC10968586
|
Treatment of MCF-7 cells with 200 μM and 400 μM OLE for 24 h produced a notable decrease in cell viability.
|
[
{
"end": 18,
"label": "CellLine",
"start": 13,
"text": "MCF-7"
}
] |
PMC10968586
|
Specifically, at a concentration of 400 μM, OLE increased MCF-7 cell death by apoptosis induction .
|
[
{
"end": 63,
"label": "CellLine",
"start": 58,
"text": "MCF-7"
}
] |
PMC10968586
|
OLE effects might depend on the upregulation of p53 and Bax, and downregulation of Bcl-2, as demonstrated by incubating MCF-7 cells with 200 μM OLE for 48 h .
|
[
{
"end": 125,
"label": "CellLine",
"start": 120,
"text": "MCF-7"
}
] |
PMC10968586
|
Other studies using a very large concentration of OLE (600 μg/mL, ≈1100 μM) shed some light on a different mechanism ruling OLE-dependent induction of apoptosis.
|
[] |
PMC10968586
|
In fact, treatment of MCF-7 cells with the mentioned OLE concentration for 48 and 72 h reduced histone deacetylase 2 (HDAC2) and HDAC3 gene transcription in a time-dependent manner , and downregulated oncomiRs miR-21 and miR-155 .
|
[
{
"end": 27,
"label": "CellLine",
"start": 22,
"text": "MCF-7"
}
] |
PMC10968586
|
However, OLE-mediated effects on ER-positive cell viability may also be appreciated at lower doses.
|
[] |
PMC10968586
|
In fact, 30 μM and 50 μM OLE were able to reduce MCF-7 cell viability after 48 h, with no significant increase in the apoptotic rate .
|
[
{
"end": 54,
"label": "CellLine",
"start": 49,
"text": "MCF-7"
}
] |
PMC10968586
|
Moreover, 150 μM OLE reduced cell viability of ER-positive MCF-7 and T47D cells after 24 h .
|
[
{
"end": 64,
"label": "CellLine",
"start": 59,
"text": "MCF-7"
},
{
"end": 73,
"label": "CellLine",
"start": 69,
"text": "T47D"
}
] |
PMC10968586
|
Further experiments on MCF-7 cell line demonstrated a dose-dependent OLE-mediated antiproliferative effect on 17β-estradiol (E2)-induced cell growth when OLE concentration was used in the range of 10–75 μM. Instead, concentrations ≥ 100 μM were found to be toxic .
|
[
{
"end": 28,
"label": "CellLine",
"start": 23,
"text": "MCF-7"
}
] |
PMC10968586
|
As regards a possible anti-estrogenic action, 10 μM OLE had no effect on estrogen receptor α (ERα) basal activation, and 10–75 μM OLE had irrelevant activity on E2-induced ERα activation and E2-modulated ERα expression, but reduced E2-induced ERK1/2 phosphorylation .
|
[] |
PMC10968586
|
In ER-positive cells, invasiveness may be suppressed by OLE-mediated induction of autophagy.
|
[] |
PMC10968586
|
In fact, treatment of MCF-7 and T47D cell lines with 100 μM OLE reversed hepatocyte growth factor (HGF)- and 3-methyladenine (3-MA, an autophagy inhibitor)-induced migration, upregulating LC3II/LC3I and Beclin1, while downregulating p62 .
|
[
{
"end": 27,
"label": "CellLine",
"start": 22,
"text": "MCF-7"
},
{
"end": 36,
"label": "CellLine",
"start": 32,
"text": "T47D"
}
] |
PMC10968586
|
OLE was also able to reduce proliferation in triple negative breast cancer cell lines MDA-MB-231 and MDA-MB-468 after 48 h incubation (IC50 = 500 μM), with RNA sequencing revealing alterations of the expression profile of genes involved in cell death, apoptosis, and response to stress .
|
[
{
"end": 96,
"label": "CellLine",
"start": 86,
"text": "MDA-MB-231"
},
{
"end": 111,
"label": "CellLine",
"start": 101,
"text": "MDA-MB-468"
}
] |
PMC10968586
|
Other reports documented that a dose as low as 50 μM was able to reduce MDA-MB-231 cell viability after 72 h incubation and IC50 = 36.2 μM was estimated for 72 h treatment .
|
[
{
"end": 82,
"label": "CellLine",
"start": 72,
"text": "MDA-MB-231"
}
] |
PMC10968586
|
A further attempt to deepen the mechanism of action in triple negative breast cancer showed that 12.5–100 μM OLE affected MDA-MB-231 cell viability in a dose- and time-dependent manner, reducing cellular migration and invasion capabilities, especially at doses ≥ 25 μM. OLE was able to induce dose-dependent apoptosis after 72 h incubation.
|
[
{
"end": 132,
"label": "CellLine",
"start": 122,
"text": "MDA-MB-231"
}
] |
PMC10968586
|
A deeper analysis, performed using a dose of 100 μM, revealed caspase-3/7 activation after 48 and 72 h, and a reduction in NF-κB phospho-p65 nuclear localization after 12 h .
|
[] |
PMC10968586
|
In a breast cancer cell line identified by the authors only by the letters “MDA”, 200 μg/mL OLE was able to interfere with the metastatic process, causing a time-dependent increase in mRNA levels of MMP inhibitors TIMP metallopeptidase inhibitor 1 (TIMP1) and TIMP3, while TIMP4 showed no further increase after 48 h incubation.
|
[
{
"end": 28,
"label": "CellLine",
"start": 5,
"text": "breast cancer cell line"
}
] |
PMC10968586
|
Simultaneously, the same concentration of OLE triggered a time-dependent decline in MMP2 and MMP9 mRNA levels .
|
[] |
PMC10968586
|
As regards HT activity in vivo, in a model of dimethylbenz[α]anthracene-induced mammary tumors in Sprague–Dawley rats treated with HT (0.5 mg/kg, 5 days/week for 6 weeks) reduced tumor growth, modulating the expression of genes involved in apoptosis and cell proliferation/survival .
|
[] |
PMC10968586
|
The relation between HT cytotoxic action in vitro and HER2 overexpression/hormone receptor status is less clear.
|
[] |
PMC10968586
|
Incubation of MCF-7 cell line with 50 μg/mL HT (≈324 μM) for 12 h was sufficient to trigger apoptosis , despite the fact that this result was not uniformly reproduced.
|
[
{
"end": 19,
"label": "CellLine",
"start": 14,
"text": "MCF-7"
}
] |
PMC10968586
|
In other experimental settings involving MCF-7 cells, the anti-proliferative activity of HT became evident at higher as well as even lower concentrations.
|
[
{
"end": 46,
"label": "CellLine",
"start": 41,
"text": "MCF-7"
}
] |
PMC10968586
|
HT used in the range of 5–400 μM for 16 h had no effect on MCF-7 cell proliferation; it became inhibited only at 600 μM .
|
[
{
"end": 64,
"label": "CellLine",
"start": 59,
"text": "MCF-7"
}
] |
PMC10968586
|
Another report documented a dose- and time-dependent effect of HT on MCF-7 cell viability, with 250 μM decreasing the percentage of viable cells after 72 h treatment, and 400 μM HT reducing cell viability as a consequence of 48 and 72 h incubation .
|
[
{
"end": 74,
"label": "CellLine",
"start": 69,
"text": "MCF-7"
}
] |
PMC10968586
|
However, at sub-lethal concentration (200 μM), HT had an impact on both (I) oxidative stress response, augmenting mRNA and protein levels of transcription factor nuclear respiratory factor 2 (Nrf2) and upregulating the transcription of its targets glutathione S-transferase alpha 2 (GSTA2) and heme oxigenase-1 (HO-1), and (II) energy homeostasis, reducing mRNA level of mitochondria biogenesis regulator PPARγ coactivator-1α (PGC-1α), while increasing its protein level and downregulating expression (in terms of mRNA) of mitochondrial function regulators estrogen-related receptor α (ERRα) and deacetylase sirtuin 3 (SIRT3) .
|
[] |
End of preview. Expand
in Data Studio
ChEMBL CellLine NER Data
Dataset Description
This dataset has been extracted from Europe PMC (EPMC), a free database offering comprehensive access to life sciences research literature. EPMC aggregates content from various sources, including PubMed, arXiv, and other repositories, and provides open access to millions of scientific articles. This dataset has been generated as part of a project collaboration between Europe PMC, Open Targets, and ChEMBL] at EMBL-EBI. Standard: Silver
Dataset Details
The dataset was extracted using assay descriptions from CheMBL andThe dataset has been annotated on mentions of cell lines. This makes it a valuable resource as it can be used for(but not limited to) the following downstream natural language processing (NLP) tasks in the biomedical domain.
NLP Tasks
Named Entity Recognition (NER): Identify and classify mentions of cell lines or related entities appearing in biomedical contexts.
Relationship Extraction: Extract relationships between cell lines and other biomedical entities, such as genes, diseases, or drugs.
Text Classification: Classify sentences or articles based on their relevance to specific cell lines, particularly in cancer research or drug development.
Sentiment Analysis: Analyze the sentiment or tone of texts discussing cell lines, such as the evaluation of experimental results (positive or negative).
Information Retrieval: Develop systems to retrieve articles or specific mentions of cell lines based on user queries.
Entity Linking: Link cell line mentions in text to standardized identifiers in cell line ontologies or databases.
Question Answering (QA): Build systems that can answer specific questions about cell lines, such as their role in particular diseases or experiments.
Topic Modeling: Analyze the dataset to uncover major themes or trends in research involving cell lines.
Text Summarization: Automatically generate summaries of articles or sections discussing cell lines.
Who funded the creation of the dataset?
Any other comments?
The dataset aims to provide a foundational resource for advancing NLP in biomedicine.
Dataset Composition
- What experiments were initially run on this dataset? No experiments have been conducted yet. Updates will follow as they occur.
Data Collection Process
How was the data collected? The dataset was collected using the Europe PMC API. Articles marked as "open access" were retrieved, and those labeled as "retraction of publication" were excluded. Duplicate entries were filtered by ensuring unique PMCIDs.
Who was involved in the data collection process? The data collection process was carried out by researchers at EMBL-EBI, leveraging automated tools for querying and processing the Europe PMC repository.
Are there any known errors, sources of noise, or redundancies in the data? None have been identified yet.
Data Preprocessing
What preprocessing/cleaning was done?
- Only open-access articles were retrieved.
- Articles labeled as "retraction of publication" were excluded.
- Duplicate entries based on the PMCID column were removed.
- Paragraph text from each section of an article was Extracted with the relevant section referenced in the 'Section Column'
- Extra whitespace, inlne math/latex formatting and irrelevant sections such "Disclosure", "Publisher's note", etc, were filtered
- Name identifiers and personal data was also removed from the dataset
Dataset Distribution
How is the dataset distributed? The dataset is freely available for use and reproduction. Proper citation of the authors is required(Information to be updated).
When will the dataset be released/first distributed? To be updated.
Dataset Maintenance
Who is supporting/hosting/maintaining the dataset?
Europe PMC, and ChEMBL team responsible for the dataset's maintenance.
How does one contact the owner/curator/manager of the dataset?
Contact can be made via the community discussion forums on GitHub or Hugging Face.
Will the dataset be updated?
Yes, updates will occur as the project progresses.
How often and by whom?
Updates will be carried out periodically by the team.
How will updates/revisions be documented and communicated?
Updates will be documented via GitHub, using version tags.
Is there a repository to link to any/all papers/systems that use this dataset?
Yes, a GitHub repository will track publications and systems using this dataset.
If others want to extend/augment/build on this dataset, is there a mechanism for them to do so?
Yes, contributions are encouraged via GitHub. Quality will be assessed through pull requests, and accepted contributions will be communicated to users via version tags and release notes.
- Downloads last month
- 46