scholarly journals Lysophospholipids activate ovarian and breast cancer cells

1995 ◽  
Vol 309 (3) ◽  
pp. 933-940 ◽  
Author(s):  
Y Xu ◽  
X J Fang ◽  
G Casey ◽  
G B Mills
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Intracellular Signaling ◽  
Breast Cancer Cells ◽  
Map Kinases ◽  
Mononuclear Cells ◽  
Phorbol Esters ◽  
Breast Cancer Cell Lines ◽  
Ovarian Cancer Cells

We have investigated the effects of phospholipids on activation and proliferation of ovarian and breast cancer cells. Lysophosphatidic acid (LPA), lysophosphatidylserine (LPS) and sphingosylphosphorylcholine (SPC) all induce transient increases in cytosolic free Ca2+ ([Ca2+]i) in both ovarian and breast cancer cell lines. The ability of LPA, LPS and SPC to induce increases in [Ca2+]i in ovarian and breast cancer cells is likely to be due to an interaction with cell-surface receptors as the increases in [Ca2+]i were: (1) due to release of calcium from intracellular stores and not from transmembrane uptake due to changes in permeability; (2) blocked by lanthanum and suramin which do not enter cells; (3) blocked by phorbol esters which interrupt increases in [Ca2+]i induced through a number of different receptors; and (4) not detected in freshly isolated peripheral blood mononuclear cells, indicating cell type specificity. In addition, increases in [Ca2+]i induced by LPA, LPS and SPC in ovarian and breast cancer cells completely self-desensitized and cross-desensitized each other, but did not block increases in [Ca2+]i induced by thrombin. Lysophosphatidylglycerol (LPG), but not other lysophospholipids, inhibited LPA- but not LPS- or SPC-induced increases in [Ca2+]i, suggesting that LPA may interact with a different receptor(s) to LPS or SPC and that their downstream signalling pathways converge or interact. LPA, SPC and LPS also induced rapid increases in tyrosine phosphorylation of specific cellular proteins, including p125FAK. Strikingly, LPA, but not LPS or SPC, induced activation of mitogen-activated protein (MAP) kinases. Despite an ability to activate similar intracellular signaling events, LPA, LPS and SPC exhibited markedly different effects on cell proliferation. Whereas LPA induced a significant increase in cell proliferation, LPS did not substantially alter cell proliferation and SPC inhibited cell proliferation. Surprisingly, phosphatidic acid (PA), which did not induce increases in [Ca2+]i, p125FAK activation or activation of MAP kinases, did induce proliferation of ovarian cancer cells, albeit at higher concentrations that LPA. The discordance between sensitivity to LPG, early biochemical events stimulated, and the eventual proliferation response combine to suggest that LPA probably utilizes a different receptor from LPS, SPC and PA. Therefore ovarian and breast cancer cells are sensitive to the effects of a number of different phospholipids which may play a role in the growth of these tumour cells in the cancer patient and are thus potential targets for therapy.

scholarly journals Highly expressed SLCO1B3 inhibits the occurrence and development of breast cancer and can be used as a clinical indicator of prognosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tiantian Tang ◽  
Guiying Wang ◽  
Sihua Liu ◽  
Zhaoxue Zhang ◽  
Chen Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines

AbstractThe role of organic anion transporting polypeptide 1B3 (SLCO1B3) in breast cancer is still controversial. The clinical immunohistochemical results showed that a greater proportion of patients with negative lymph nodes, AJCC stage I, and histological grade 1 (P < 0.05) was positively correlated with stronger expression of SLCO1B3, and DFS and OS were also increased significantly in these patients (P = 0.041, P = 0.001). Further subgroup analysis showed that DFS and OS were significantly enhanced with the increased expression of SLCO1B3 in the ER positive subgroup. The cellular function assay showed that the ability of cell proliferation, migration and invasion was significantly enhanced after knockdown of SLCO1B3 expression in breast cancer cell lines. In contrast, the ability of cell proliferation, migration and invasion was significantly reduced after overexpress the SLCO1B3 in breast cancer cell lines (P < 0.05). Overexpression or knockdown of SLCO1B3 had no effect on the apoptotic ability of breast cancer cells. High level of SLCO1B3 expression can inhibit the proliferation, invasion and migration of breast cancer cells, leading to better prognosis of patients. The role of SLCO1B3 in breast cancer may be related to estrogen. SLCO1B3 will become a potential biomarker for breast cancer diagnosis and prognosis assessment.

scholarly journals The role of protein kinase PAK1 in the regulation of estrogen-independent growth of breast cancer

2014 ◽  
Vol 60 (3) ◽  
pp. 322-331 ◽  
Author(s):  
E.A. Avilova ◽  
O.E. Andreeva ◽  
V.A. Shatskaya ◽  
M.A. Krasilnikov
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Intracellular Signaling ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Breast Cancer Cell Lines ◽  
Hormone Resistance ◽  
Mesenchymal Transition

The main goal of this work was to study the intracellular signaling pathways responsible for the development of hormone resistance and maintaining the autonomous growth of breast cancer cells. In particular, the role of PAK1 (p21-activated kinase 1), the key mitogenic signaling protein, in the development of cell resistance to estrogens was analyzed. In vitro studies were performed on cultured breast cancer cell lines: estrogen-dependent estrogen receptor (ER)-positive MCF-7 cells and estrogen-resistant ER-negative HBL-100 cells. We found that the resistant HBL-100 cells were characterized by a higher level of PAK1 and demonstrated PAK1 involvement in the maintaining of estrogen-independent cell growth. We have also shown PAK1 ability to up-regulate Snail1, one of the epithelial-mesenchymal transition proteins, and obtained experimental evidence for Snail1 importance in the regulation of cell proliferation. In general, the results obtained in this study demonstrate involvement of PAK1 and Snail1 in the formation of estrogen-independent phenotype of breast cancer cells showing the potential role of both proteins as markers of hormone resistance of breast tumors.

scholarly journals The Effects of Houttuynia cordata Thunb and Piper ribesioides Wall Extracts on Breast Carcinoma Cell Proliferation, Migration, Invasion and Apoptosis

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1196 ◽  
Author(s):  
Subhawat Subhawa ◽  
Teera Chewonarin ◽  
Ratana Banjerdpongchai
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines ◽  
Houttuynia Cordata ◽  
Houttuynia Cordata Thunb

Houttuynia cordata Thunb. (HCT) and Piper ribesioides Wall. (PR) are common herbs that are widely distributed throughout East Asia and possess various biological properties including anti-cancer effects. However, in breast cancer, their mechanisms responsible for anti-carcinogenic effects have not been clarified yet. In this study, the inhibitory effects of HCT and PR ethanolic extracts on breast cancer cell proliferation, migration, invasion and apoptosis were examined. In MCF-7 and MDA-MB-231 cells, HCT and PR extracts at low concentrations can inhibit colony formation and induce G1 cell cycle arrest by downregulating cyclinD1 and CDK4 expression. Additionally, HCT and PR extracts also decreased the migration and invasion of both breast cancer cell lines through inhibition of MMP-2 and MMP-9 secretion. Moreover, the induction of apoptosis was observed in breast cancer cells treated with high concentrations of HCT and PR extracts. Not only stimulated caspases activity, but HCT and PR extracts also upregulated the expression of caspases and pro-apoptotic Bcl-2 family proteins in breast cancer cells. Altogether, these findings provide the rationale to further investigate the potential actions of HCT and PR extracts against breast cancer in vivo.

Synthesis and In Vitro Evaluation of Tetrahydroquinoline Derivatives as Antiproliferative Compounds of Breast Cancer via Targeting the GPER

2019 ◽  
Vol 19 (6) ◽  
pp. 760-771 ◽  
Author(s):  
Oscar J. Zacarías-Lara ◽  
David Méndez-Luna ◽  
Gustavo Martínez-Ruíz ◽  
José R. García-Sanchéz ◽  
Manuel J. Fragoso-Vázquez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cell Lines ◽  
In Silico ◽  
Breast Cancer Cells ◽  
Breast Cancer Cell Lines ◽  
In Silico Studies ◽  
Mcf 7

Background: Some reports have demonstrated the role of the G Protein-coupled Estrogen Receptor (GPER) in growth and proliferation of breast cancer cells. Objective: In an effort to develop new therapeutic strategies against breast cancer, we employed an in silico study to explore the binding modes of tetrahydroquinoline 2 and 4 to be compared with the reported ligands G1 and G1PABA. Methods: This study aimed to design and filter ligands by in silico studies determining their Lipinski's rule, toxicity and binding properties with GPER to achieve experimental assays as anti-proliferative compounds of breast cancer cell lines. Results: In silico studies suggest as promissory two tetrahydroquinoline 2 and 4 which contain a carboxyl group instead of the acetyl group (as is needed for G1 synthesis), which add low (2) and high hindrance (4) chemical moieties to explore the polar, hydrophobic and hindrance effects. Docking and molecular dynamics simulations of the target compounds were performed with GPER to explore their binding mode and free energy values. In addition, the target small molecules were synthesized and assayed in vitro using breast cancer cells (MCF-7 and MDA-MB-231). Experimental assays showed that compound 2 decreased cell proliferation, showing IC50 values of 50µM and 25µM after 72h of treatment of MCF-7 and MDA-MB-231 cell lines, respectively. Importantly, compound 2 showed a similar inhibitory effect on proliferation as G1 compound in MDA-MB-231 cells, suggesting that both ligands reach the GPER-binding site in a similar way, as was demonstrated through in silico studies. Conclusion: A concentration-dependent inhibition of cell proliferation occurred with compound 2 in the two cell lines regardless of GPER.

scholarly journals α-Mangostin Synergizes the Antineoplastic Effects of 5-Fluorouracil Allowing a Significant Dose Reduction in Breast Cancer Cells

Processes ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 458
Author(s):  
Galia Lara-Sotelo ◽  
Lorenza Díaz ◽  
Rocío García-Becerra ◽  
Euclides Avila ◽  
Heriberto Prado-Garcia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Dose Reduction ◽  
Breast Cancer Cells ◽  
Breast Cancer Cell Lines ◽  
Dependent Manner ◽  
Pharmacological Interaction ◽  
Dose Reduction Index ◽  
Reduction Index

Breast cancer is the most common neoplasm and the leading cause of cancer death in women worldwide. Although 5-fluorouracil is a conventional chemotherapeutic agent for breast cancer treatment, its use may result in severe side effects. Thus, there is widespread interest in lowering 5-fluorouracil drawbacks, without affecting its therapeutic efficacy by the concomitant use with natural products. Herein, we aimed at evaluating whether α-mangostin, a natural antineoplastic compound, could increase the anticancer effect of 5-fluorouracil in different breast cancer cell lines, allowing for dose reduction. Cell proliferation was evaluated by sulforhodamine-B assays, inhibitory concentrations and potency were calculated by dose-response curves, followed by analysis of their pharmacological interaction by the combination-index method and dose-reduction index. Cell cycle distribution was evaluated by flow cytometry. Each compound inhibited cell proliferation in a dose-dependent manner, the triple negative breast cancer cells being the most sensitive. When 5-fluorouracil and α-mangostin were used concomitantly, synergistic antiproliferative effect was observed. The calculated dose-reduction index suggested that this combination exhibits therapeutic potential for reducing 5-fluorouracil dosage in breast cancer. Mechanistically, the cotreatment induced cell death in a greater extent than each drug alone. Therefore, α-mangostin could be used as a potent co-adjuvant for 5-fluorouracil in breast cancer.

scholarly journals Knockdown of CD-74 in the Proliferative and Apoptotic Activity of Breast Cancer Cells

2019 ◽  
Vol 7 (19) ◽  
pp. 3169-3176
Author(s):  
Hussain Al Ssadh ◽  
Waleed Al Abdulmonem ◽  
Zafar Rasheed ◽  
Inamul Hasan Madar ◽  
Jamila Alhoderi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cell Lines ◽  
Breast Cancer Cells ◽  
Surrogate Marker ◽  
Tumour Marker ◽  
Breast Cancer Cell Lines ◽  
Proliferation And Apoptosis ◽  
Apoptotic Activity

BACKGROUND: The cluster of differentiation (CD) 74 is known for its immunological functions and its elevated level was reported in various cancer cells. AIM: The aim of the present study was to investigate the expression and potential roles of CD74 in the proliferative and apoptotic activity of breast cancer. METHODS: Expression of CD74, macrophage migration inhibitory factor (MIF) and CD44 was assayed in CAMA-1 and MDA-MB-231 cell lines using flow cytometry. CD74 was knocked down using CD74 siRNA-transfection in CAMA-1, and MDA-MB-231 cells and proliferation and apoptosis were determined in the transfected breast cancer cells. RESULTS: The data showed that CD74, MIF and CD44 were expressed in breast cancer cell lines and were associated with cell proliferation and apoptosis. Correlation analysis revealed that CD74 was positively correlated and colocalised with MIF on the cell-surface of CAMA-1 and MDA-MB-231. The knockdown of CD74 significantly reduced CAMA-1 and MDA-MB-231 cell proliferation and increased the level of apoptotic cells. CONCLUSION: We concluded that the interactions of CD74 with MIF and CD74 with CD44 could be a potential tumour marker for breast cancer cells. Moreover, the level of co-expression of MIF and CD74 or CD44 could be a surrogate marker for the efficacy of anti-angiogenic drugs, particularly in breast cancer tumours. In short, the study revealed the potential roles of CD74 in the proliferation and apoptosis of breast cancer which may serve as a potential therapeutic target for breast cancer.

Effect of enzastaurin on cell signaling, proliferation and apoptosis in breast cancer cell lines

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14121-14121
Author(s):  
B. Spankuch ◽  
E. Kurunci-Csacsko ◽  
T. Bauknecht ◽  
K. Strebhardt
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Caspase 9

14121 Background: Enzastaurin, an acyclic bisindolylmaleimide, is a potent selective serine/threonine kinase inhibitor that inhibits PKCβ, targets the PI3K/AKT pathway, and inhibits GSK3β phosphorylation. Enzastaurin induced apoptosis and decreased proliferation of various cancer lines, and decreased VEGF expression and microvessel density in human tumor xenografts. In animal models, enzastaurin had antitumor/antiangiogenic activity in non-small-cell lung, colon, renal cell, hepatocellular, and other cancers. Therefore, we sought to determine enzastaurin’s impact on cellular PKCβ-mediated signaling in breast cancer cells. Secondarily, we sought to determine the induction of the apoptotic cascade by enzastaurin. Methods: Breast cancer cell lines MCF-7, BT-474, MDA-MB-435 and SK-BR-3 were treated with differing enzastaurin concentrations. Western-Blot analyses were performed to examine PKCβ, phospho-GSK3β and caspase 9 expressions. The phenotype and proliferation of enzastaurin-treated cells were also monitored by fluorescence microscopy. Results: Treating all 4 cancer cell lines with ascending enzastaurin doses (0.1–10 μM) led to a significant downregulation of GSK3β phosphorylation (2–17%) compared to control cells. A 48–72 hr incubation with increasing enzastaurin doses also reduced the PKCβ expression significantly (5–50%). Moreover, a dose- dependent reduction of cell proliferation to levels of 15–40% compared to control cells with the highest enzastaurin concentration was detectable. We also saw a marked pro-caspase 9 reduction (0–30%) after enzastaurin compared to control cells. The microscopic inspection of treated cells phenotypically confirmed increasing apoptosis-induced cell death. Conclusions: Enzastaurin has a significant antiproliferative effect in different breast cancer cells. Moreover, enzastaurin suppresses GSK3β phosphorylation, suggesting that it may be a reliable pharmacodynamic marker for enzastaurin activity in breast cancer cells; however, more preclinical analysis is needed. Our study provides evidence for enzastaurin’s potential to directly suppress breast cancer cell proliferation and to induce tumor cell death by apoptotic induction. No significant financial relationships to disclose.

scholarly journals miR-301b-3p Regulates Breast Cancer Cell Proliferation, Migration, and Invasion by Targeting NR3C2

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yaohua Fan ◽  
Yan Li ◽  
Yuzhang Zhu ◽  
Guiping Dai ◽  
Dongjuan Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines ◽  
Cancer Cell Proliferation

Objectives. Breast cancer is the most common malignant tumor among females, and miRNAs have been reported to play an important regulatory role in breast cancer progression. This study aimed to explore the function and underlying molecular mechanism of miR-301b-3p in breast cancer. Methods. Differential analysis and survival analysis were performed based on the data accessed from the TCGA-BRCA dataset for identification of the target miRNA. Bioinformatics analysis was conducted to predict the downstream target gene of the miRNA. Real-time quantitative PCR was carried out to detect the expression of miR-301b-3p and nuclear receptor subfamily 3 group C member 2 (NR3C2). Western blot was used to assess the protein expression of NR3C2. Cell counting kit-8 assay was performed to evaluate the proliferation of breast cancer cells. Transwell assay was conducted to determine the migratory and invasive abilities of breast cancer cells. Dual-luciferase reporter assay was employed to verify the targeting relationship between miR-301b-3p and NR3C2. Results. miR-301b-3p was elevated in breast cancer cell lines and promoted cell proliferation, migration, and invasion in terms of its biological function in breast cancer. NR3C2 was validated as a direct target of miR-301b-3p via bioinformatics analysis and dual-luciferase reporter assay, and NR3C2 was downregulated in breast cancer cell lines. The rescue experiment indicated that NR3C2 was involved in the mechanism by which miR-301b-3p regulated the malignant phenotype of breast cancer cells. Conclusion. The present study revealed for the first time that miR-301b-3p could foster breast cancer cell proliferation, migration, and invasion by targeting NR3C2, unveiling that miR-301b-3p is a novel carcinogen in breast cancer.

scholarly journals AKR1B10 promotes breast cancer cell proliferation and migration via the PI3K/AKT/NF-κB signaling pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jiayao Qu ◽  
Jia Li ◽  
Yaming Zhang ◽  
Rongzhang He ◽  
Xiangting Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines ◽  
Related Proteins ◽  
Mcf 7

Abstract Background Aberrant expression of Aldo-Keto reductase family 1 member B10 (AKR1B10) was associated with tumor size and metastasis of breast cancer in our published preliminary studies. However, little is known about the detailed function and underlying molecular mechanism of AKR1B10 in the pathological process of breast cancer. Methods The relationship between elevated AKR1B10 expression and the overall survival and disease-free survival of breast cancer patients was analyzed by Kaplan–Meier Plotter database. Breast cancer cell lines overexpressing AKR1B10 (MCF-7/AKR1B10) and breast cancer cell lines with knockdown of AKR1B10 (BT-20/shAKR1B10) were constructed to analyze the impact of AKR1B10 expression on cell proliferation and migration of breast cancer. The expression levels of AKR1B10 were detected and compared in the breast cancer cell lines and tissues by RT-qPCR, western blot and immunohistochemistry. The proliferation of breast cancer cells was monitored by CCK8 cell proliferation assay, and the migration and invasion of breast cancer cells was observed by cell scratch test and transwell assay. The proliferation- and EMT-related proteins including cyclinD1, c-myc, Survivin, Twist, SNAI1, SLUG, ZEB1, E-cadherin, PI3K, p-PI3K, AKT, p-AKT, IKBα, p-IKBα, NF-κB p65, p-NF-κB p65 were detected by western blot in breast cancer cells. MCF-7/AKR1B10 cells were treated with LY294002, a PI3K inhibitor, to consider the impact of AKR1B10 overexpression on the PI3K/AKT/NF-κB signal cascade and the presence of NF-κB p65 in nuclear. In vivo tumor xenograft experiments were used to observe the role of AKR1B10 in breast cancer growth in mice. Results AKR1B10 expression was significantly greater in breast cancer tissue compared to paired non-cancerous tissue. The expression of AKR1B10 positively correlated with lymph node metastasis, tumor size, Ki67 expression, and p53 expression, but inversely correlated with overall and disease-free survival rates. Gene Ontology analysis showed that AKR1B10 activity contributes to cell proliferation. Overexpression of AKR1B10 facilitated the proliferation of MCF-7 cells, and induced the migration and invasion of MCF-7 cells in vitro in association with induction of epithelial-mesenchymal transition (EMT). Conversely, knockdown of AKR1B10 inhibited these effects in BT-20 cells. Mechanistically, AKR1B10 activated PI3K, AKT, and NF-κB p65, and induced nuclear translocation of NF-κB p65, and expression of proliferation-related proteins including c-myc, cyclinD1, Survivin, and EMT-related proteins including ZEB1, SLUG, Twist, but downregulated E-cadherin expression in MCF-7 cells. AKR1B10 silencing reduced the phosphorylation of PI3K, AKT, and NF-κB p65, the nuclear translocation of NF-κB p65, and the expression of proliferation- and migration-related proteins in BT-20 cells. LY294002, a PI3K inhibitor, attenuated the phosphorylation of PI3K, AKT, and NF-κB p65, and the nuclear translocation of NF-κB p65. In vivo tumor xenograft experiments confirmed that AKR1B10 promoted breast cancer growth in mice. Conclusions AKR1B10 promotes the proliferation, migration and invasion of breast cancer cells via the PI3K/AKT/NF-κB signaling pathway and represents a novel prognostic indicator as well as a potential therapeutic target in breast cancer.

Sign in / Sign up

Export Citation Format

Share Document