Telomerase Inhibitor TMPyP4 Alters Adhesion and Migration of Breast-Cancer Cells MCF7 and MDA-MB-231

Konieczna, Natalia; Romaniuk-Drapała, Aleksandra; Lisiak, Natalia; Totoń, Ewa; Paszel-Jaworska, Anna; Kaczmarek, Mariusz; Rubiś, Błażej

doi:10.3390/ijms20112670

Cited by 32 publications

(26 citation statements)

References 41 publications

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“…20 TMPyP4, a telomerase inhibitor, significantly inhibited the migration and adhesion of some breast cancer cells (MCF-7 and MDA-MB-231). 21 Similar to the results of these studies, treatment of AC and co-treatment of AC+PAC or SV+PAC significantly inhibited the migration of MCF-7 cells in our study.…”

Section: Discussionsupporting

confidence: 91%

Effects of Reverse Transcriptase Inhibitors on Proliferation, Apoptosis, and Migration in Breast Carcinoma Cells

Şekeroğlu

Küçük

2020

Int J Toxicol

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High telomerase activity in human breast cancer is associated with aggressive tumors resulting in decreased survival. Recent studies have shown that telomerase inhibitors may display anticancer properties in some human cancer cell lines. In the present study, we examined the effects of 4 reverse transcriptase inhibitors (RTIs), used for the treatment of HIV; Abacavir (AC), Lamivudine (LV), Stavudine (SV), and Tenofovir (TF) on proliferation, apoptosis, and migration in the normal human mammary epithelial cell line, hTERT-HME1, and the human breast cancer cell line, MCF-7. Cells were treated with AC, LV, SV, or TF alone or in combination with paclitaxel (PAC), a known drug used to treat breast cancer. Conduct of the thiazolyl blue tetrazolium bromide assay demonstrated that AC, SV, and TF had stronger cytotoxic effects on MCF-7 cells than in hTERT-HME1 cells. The combined treatment of RTIs and PAC caused high rates of cell death in MCF-7 and low rates of cell death in HTERT-HME1 by apoptosis. The percentages of apoptotic cells in the treatment of AC and SV in combination with PAC for 48 and 72 hours were higher than PAC. Significantly increased apoptosis and decreased migration levels were found in MCF-7 cells treated with AC and co-treatment of AC+PAC or SV+PAC than HME1 cells. These treatments can also prevent migration capacity more than PAC. Therefore, a combination strategy based on telomerase inhibitors such as AC or SV and anticancer drugs may be more effective in the treatment of certain breast cancers.

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Section: Discussionsupporting

confidence: 91%

Effects of Reverse Transcriptase Inhibitors on Proliferation, Apoptosis, and Migration in Breast Carcinoma Cells

Şekeroğlu

Küçük

2020

Int J Toxicol

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“…An early approach was to design compounds that would interact with DNA at the 3’ overhang, stabilizing telomeric G-quadruplex secondary structures, and thus blocking telomerase access to DNA. Telomestatin, BRACO-19, RHPS4, TMPyP4 are some of the most commonly studied G-quadruplex binding proteins ( 191 , 196 , 197 ). Telomestatin (OBP-301) is a natural product isolated from Streptomyces anulatus ( 198 ).…”

Section: Tert As a Potential Therapeutic Targetmentioning

confidence: 99%

“…These DNA-binding compounds are now less popular due to discovery of better molecular strategies, such as targeting the TERT active site directly. Studies on such inhibitors led to discovery of 2-[[(E)-3-naphthalen-2-ylbut-2-enoyl]amino]benzoic acid (BIBR1532), which inhibits telomerase by binding non-competitively to the TERT active site ( 197 , 200 ). This binding leads to increased oxidative stress and decreased nitrogen monoxide bioavailability in favor of H 2 O 2 .…”

Section: Tert As a Potential Therapeutic Targetmentioning

confidence: 99%

TERT—Regulation and Roles in Cancer Formation

et al. 2020

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Telomerase reverse transcriptase (TERT) is a catalytic subunit of telomerase. Telomerase complex plays a key role in cancer formation by telomere dependent or independent mechanisms. Telomere maintenance mechanisms include complex TERT changes such as gene amplifications, TERT structural variants, TERT promoter germline and somatic mutations, TERT epigenetic changes, and alternative lengthening of telomere. All of them are cancer specific at tissue histotype and at single cell level. TERT expression is regulated in tumors via multiple genetic and epigenetic alterations which affect telomerase activity. Telomerase activity via TERT expression has an impact on telomere length and can be a useful marker in diagnosis and prognosis of various cancers and a new therapy approach. In this review we want to highlight the main roles of TERT in different mechanisms of cancer development and regulation.

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“…After identification of the IC 50 of the crude extracts and 10K fractions (10.32 and 11.53 µg/mL, respectively) and cell treatment, nonetheless, in this time frame, the sole modification observed was the occurrence of mitochondrial depolarization in the presence of the crude extract down to percentages close to those of the corresponding positive control, whereas there was no difference between treated and control cells in all the other assays. The late occurrence of the phenotypic effects observed, i.e., after 48 h of exposure to CF extracts, is in line with the widely recognized resistance of the MDA-MB231 cell line to treatments and its delayed responses [33,34]. In the light of such preliminary evidence, we decided to examine, in detail, only the effects after 48 h of exposure.…”

Section: Discussionmentioning

confidence: 93%

Cell-Free Coelomic Fluid Extracts of the Sea Urchin Arbacia lixula Impair Mitochondrial Potential and Cell Cycle Distribution and Stimulate Reactive Oxygen Species Production and Autophagic Activity in Triple-Negative MDA-MB231 Breast Cancer Cells

Luparello

Ragona

Asaro

et al. 2020

JMSE

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Triple-negative breast cancer (TNBC) is a highly malignant tumor histotype which lacks effective targeted therapies, thereby being considered as the most aggressive form of breast carcinoma. To identify novel compounds which could counteract TNBC cell growth, we explored the in vitro effects of crude extracts and <10 kDa-filtered fractions of the coelomic fluid obtained from the sea urchin Arbacia lixula on TNBC MDA-MB231 cells. We examined cell viability, cycle distribution, apoptotic/autophagic activity, and mitochondrial polarization/cell redox status. Here, we report the first data demonstrating an anti-TNBC effect by A. lixula-derived coelomic fluid extracts. Thus, identification of the water-soluble bioactive component(s) contained in the extracts deserve(s) further investigation aimed to devise novel promising prevention and/or treatment agents effective against highly malignant breast tumors.Further studies conducted by Björn et al. [8] demonstrated that the synthetic peptides sequentially derived from the previously characterized centrocin 1 (CEN1 HC-Br and CEN1 HC) showed prominent microbicidal and anti-inflammatory activities on in vivo and in vitro mammalian models, representing an interesting resource for the treatment of infections in humans.Furthermore, a recent study by Katelnikova et al. [9] highlighted that a glycopeptide fraction (GPF) derived from internal organs of the green sea urchins Strongylocentrotus droebachiensis possesses relevant anti-inflammatory effects, especially for the treatment of bronchitis. Moreover, the absorption and pharmacokinetics of GPF following single and repeated intranasal administration were evaluated over the course of seven days in rats [10].Another echinoderm species from which bioactive molecules were studied is Arbacia lixula, commonly found in the Mediterranean Sea and in the African Atlantic coast [11]. So far, the biomedical applications of molecules extracted from this marine invertebrate are very limited. Of note, Stabili et al. [12] demonstrated the powerful antioxidant effect exerted by the lysate of A. lixula's coelomocytes, the immune cells present in the coelomic fluid (CF) of the sea urchin, whereas Cirino et al. [13] highlighted that A. lixula's eggs are a rich source of astaxanthin, a radical scavenger that can prevent neurodegenerative diseases. These promising findings prompted an extension of the study on the pharmacological potential of A. lixula-derived substances, whose massive sourcing represents an easy task due to the abundance of this marine species in waters surrounding Sicily, also being a thermophilic species which is expanding very quickly due to the increase of the surface temperature of the Mediterranean Sea [14].Triple-negative breast cancers (TNBC) are categorized among the highly "aggressive" malignant carcinomas. In fact, the lack of expression of estrogen, progesterone, and epidermal growth factor type 2 (HER2) receptors makes them poorly responsive to hormonal therapies and to HER2-targeting drugs, and the TNBC histotype ...

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Telomerase Inhibitor TMPyP4 Alters Adhesion and Migration of Breast-Cancer Cells MCF7 and MDA-MB-231

Cited by 32 publications

References 41 publications

Effects of Reverse Transcriptase Inhibitors on Proliferation, Apoptosis, and Migration in Breast Carcinoma Cells

Effects of Reverse Transcriptase Inhibitors on Proliferation, Apoptosis, and Migration in Breast Carcinoma Cells

TERT—Regulation and Roles in Cancer Formation

Cell-Free Coelomic Fluid Extracts of the Sea Urchin Arbacia lixula Impair Mitochondrial Potential and Cell Cycle Distribution and Stimulate Reactive Oxygen Species Production and Autophagic Activity in Triple-Negative MDA-MB231 Breast Cancer Cells

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