scholarly journals Evaluation of the antiproliferative effects of the HASPIN inhibitor CHR-6494 in breast cancer cell lines

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249912
Author(s):  
Hisayo Nishida-Fukuda ◽  
Keizo Tokuhiro ◽  
Yukio Ando ◽  
Hiroaki Matsushita ◽  
Morimasa Wada ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Mammary Epithelial Cells ◽  
Cancer Cell Lines ◽  
Mammary Epithelial ◽  
Breast Cancer Cell Lines ◽  
Antiproliferative Effects

HASPIN is a serine/threonine kinase that regulates mitosis by phosphorylating histone H3 at threonine 3. The expression levels of HASPIN in various cancers are associated with tumor malignancy and poor survival, suggesting that HASPIN inhibition may suppress cancer growth. As HASPIN mRNA levels are elevated in human breast cancer tissues compared with adjacent normal tissues, we examined the growth-suppressive effects of CHR-6494, a potent HASPIN inhibitor, in breast cancer cell lines in vitro and in vivo. We found that HASPIN was expressed in breast cancer cells of all molecular subtypes, as well as in immortalized mammary epithelial cells. HASPIN expression levels appeared to be correlated with the cell growth rate but not the molecular subtype of breast cancer. CHR-6494 exhibited potent antiproliferative effects against breast cancer cell lines and immortalized mammary epithelial cells in vitro, but failed to inhibit the growth of MDA-MB-231 xenografted tumors under conditions that have significant effects in a colorectal cancer model. These results imply that CHR-6494 does have antiproliferative effects in some situations, and further drug screening efforts are anticipated to identify more potent and selective HASPIN inhibition for use as an anticancer agent in breast cancer patients.

scholarly journals Profiling Flavonoid Cytotoxicity in Human Breast Cancer Cell Lines: Determination of Structure-Function Relationships

2012 ◽  
Vol 7 (10) ◽  
pp. 1934578X1200701 ◽  
Author(s):  
Sina Yadegarynia ◽  
Anh Pham ◽  
Alex Ng ◽  
Duong Nguyen ◽  
Tetiana Lialiutska ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Mammary Epithelial Cells ◽  
Cancer Cell Lines ◽  
Mammary Epithelial ◽  
Breast Cancer Cell Lines ◽  
Mitochondrial Outer Membrane ◽  
Outer Membrane Permeability

Flavonoids have been shown to be cytotoxic to cancer cells. However, the mechanism of cytotoxicity has not been clearly defined. It has previously been reported that HER2/ERBB2, the estrogen receptor, progesterone receptor, and p53 were required for flavonoid induced cytotoxicity in breast cancer cell lines. We have used a panel of breast cancer cell lines, known to contain as well as be deficient in these signaling pathways, to screen fourteen different flavonoids. Comparing the cytotoxicity for all flavonoids allows us to determine if a structure-functional relationship exists between cytotoxicity and flavonoid, and if a particular signaling pathway is required for cytotoxicity. We show that several flavonoids are cytotoxic to all cell lines including primary mammary epithelial cells tested. The cytotoxic flavonoids are also able to inhibit Mitochondrial Outer Membrane Permeability while at the same time stimulate ATP levels whereas the non-cytotoxic flavonoids are not able to do this. We also show that both cytotoxic and non-cytotoxic flavonoids can transverse the cell membrane to enter MDA-MB-231 cells at different levels. Finally, all flavonoids regardless of their cytotoxicity were able to induce some form of cell cycle arrest. We conclude that for flavonoids to be strongly cytotoxic, they must possess the 2,3-double bond in the C-ring and we believe the cytotoxicity occurs through mitochondrial poisoning in both cancer and normal cells.

Synthesis, Characterization and In Vitro Antiproliferative Effects of Novel 5-Amino Pyrazole Derivatives against Breast Cancer Cell Lines

2011 ◽  
Vol 6 (2) ◽  
pp. 186-195 ◽  
Author(s):  
Hanumegowda Raju ◽  
Siddappa Chandrappa ◽  
Doddakunche S. Prasanna ◽  
Hanumappa Ananda ◽  
Tandaga S. Nagamani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Pyrazole Derivatives ◽  
Antiproliferative Effects

The arotinoid Ro 40-8757 has antiproliferative effects in drug-resistant human colon and breast cancer cell lines in vitro

1994 ◽  
Vol 85 (1) ◽  
pp. 83-86 ◽  
Author(s):  
Christophe Louvet ◽  
Sylvie Empereur ◽  
Dominique Fagot ◽  
Elisabeth Forgue-Lafitte ◽  
Eric Chastre ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Human Colon ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Drug Resistant ◽  
Antiproliferative Effects

scholarly journals Profiling Flavonoid Cytotoxicity in Human Breast Cancer Cell Lines: Determination of Structure-Function Relationships

2014 ◽  
Vol 9 (5) ◽  
pp. 1934578X1400900 ◽  
Author(s):  
Sina Yadegarynia ◽  
Anh Pham ◽  
Alex Ng ◽  
Duong Nguyen ◽  
Tetiana Lialiutska ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Mammary Epithelial Cells ◽  
Cancer Cell Lines ◽  
Mammary Epithelial ◽  
Breast Cancer Cell Lines ◽  
Mitochondrial Outer Membrane ◽  
Outer Membrane Permeability

Flavonoids have been shown to be cytotoxic to cancer cells. However, the mechanism of cytotoxicity has not been clearly defined. It has previously been reported that HER2/ERBB2, the estrogen receptor, progesterone receptor, and p53 were required for flavonoid induced cytotoxicity in breast cancer cell lines. We have used a panel of breast cancer cell lines, known to contain as well as be deficient in these signaling pathways, to screen fourteen different flavonoids. Comparing the cytotoxicity for all flavonoids allows us to determine if a structure-functional relationship exists between cytotoxicity and flavonoid, and if a particular signaling pathway is required for cytotoxicity. We show that several flavonoids are cytotoxic to all cell lines including primary mammary epithelial cells tested. The cytotoxic flavonoids are also able to inhibit Mitochondrial Outer Membrane Permeability while at the same time stimulate ATP levels whereas the non-cytotoxic flavonoids are not able to do this. We also show that both cytotoxic and non-cytotoxic flavonoids can transverse the cell membrane to enter MDA-MB-231 cells at different levels. Finally, all flavonoids regardless of their cytotoxicity were able to induce some form of cell cycle arrest. We conclude that for flavonoids to be strongly cytotoxic, they must possess the 2,3-double bond in the C-ring and we believe the cytotoxicity occurs through mitochondrial poisoning in both cancer and normal cells.

scholarly journals Oncogenic PIK3CA mutations increase dependency on the mRNA cap methyltransferase, RNMT, in breast cancer cells

Open Biology ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 190052 ◽  
Author(s):  
Sianadh Dunn ◽  
Olivia Lombardi ◽  
Radoslaw Lukoszek ◽  
Victoria H. Cowling
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Mammary Epithelial Cells ◽  
Cancer Therapeutics ◽  
Cancer Cell Lines ◽  
Mammary Epithelial ◽  
Breast Cancer Cell Lines ◽  
Pik3ca Mutations

Basic mechanisms in gene expression are currently being investigated as targets in cancer therapeutics. One such fundamental process is the addition of the cap to pre-mRNA, which recruits mediators of mRNA processing and translation initiation. Maturation of the cap involves mRNA cap guanosine N-7 methylation, catalysed by RNMT (RNA guanine-7 methyltransferase). In a panel of breast cancer cell lines, we investigated whether all are equivalently dependent on RNMT for proliferation. When cellular RNMT activity was experimentally reduced by 50%, the proliferation rate of non-transformed mammary epithelial cells was unchanged, whereas a subset of breast cancer cell lines exhibited reduced proliferation and increased apoptosis. Most of the cell lines which exhibited enhanced dependency on RNMT harboured oncogenic mutations in PIK3CA, which encodes the p110α subunit of PI3Kα. Conversely, all cell lines insensitive to RNMT depletion expressed wild-type PIK3CA. Expression of oncogenic PIK3CA mutants, which increase PI3K p110α activity, was sufficient to increase dependency on RNMT. Conversely, inhibition of PI3Kα reversed dependency on RNMT, suggesting that PI3Kα signalling is required. Collectively, these findings provide evidence to support RNMT as a therapeutic target in breast cancer and suggest that therapies targeting RNMT would be most valuable in a PIK3CA mutant background.

ANTITUMOR EFFECT OF SUNITINIB AND BORTEZOMIB ON BREAST CANCER CELL LINE IN VITRO

2017 ◽  
Vol 63 (1) ◽  
pp. 141-145
Author(s):  
Yuliya Khochenkova ◽  
Eliso Solomko ◽  
Oksana Ryabaya ◽  
Yevgeniya Stepanova ◽  
Dmitriy Khochenkov
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Antitumor Effect ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Actual Problem

The discovery for effective combinations of anticancer drugs for treatment for breast cancer is the actual problem in the experimental chemotherapy. In this paper we conducted a study of antitumor effect of the combination of sunitinib and bortezomib against MDA-MB-231 and SKBR-3 breast cancer cell lines in vitro. We found that bortezomib in non-toxic concentrations can potentiate the antitumor activity of sunitinib. MDA-MB-231 cell line has showed great sensitivity to the combination of bortezomib and sunitinib in vitro. Bortezomib and sunitinib caused reduced expression of receptor tyrosine kinases VEGFR1, VEGFR2, PDGFRa, PDGFRß and c-Kit on HER2- and HER2+ breast cancer cell lines

Small Molecular Leads Differentially Active Against HER2 Positive and Triple Negative Breast Cancer Cell Lines

2019 ◽  
Vol 15 (7) ◽  
pp. 738-742 ◽  
Author(s):  
Adnan Badran ◽  
Atia-tul-Wahab ◽  
Sharmeen Fayyaz ◽  
Elias Baydoun ◽  
Muhammad Iqbal Choudhary
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Triple Negative ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Cancer Type

Background:Breast cancer is the most prevalent cancer type in women globally. It is characterized by distinct subtypes depending on different gene expression patterns. Oncogene HER2 is expressed on the surface of cell and is responsible for cell growth regulation. Increase in HER2 receptor protein due to gene amplification, results in aggressive growth, and high metastasis in cancer cells.Methods:The current study evaluates and compares the anti-breast cancer effect of commercially available compounds against HER2 overexpressing BT-474, and triple negative MDA-MB-231 breast cancer cell lines.Results:Preliminary in vitro cell viability assays on these cell lines identified 6 lead molecules active against breast cancer. Convallatoxin (4), a steroidal lactone glycoside, showed the most potent activity with IC50 values of 0.63 ± 0.56, and 0.69 ± 0.59 µM against BT-474 and MDA-MB-231, respectively, whereas 4-[4-(Trifluoromethyl)-phenoxy] phenol (3) a phenol derivative, and Reserpine (5) an indole alkaloid selectively inhibited the growth of BT-474, and MDA-MB-231 breast cancer cells, respectively.Conclusion:These results exhibited the potential of small molecules in the treatment of HER2 amplified and triple negative breast cancers in vitro.

The α2δ1 subunit of the voltage-gated calcium channel as a potential candidate for breast cancer tumor initial cells biomarker

2021 ◽  
pp. 1-11
Author(s):  
Meng Li ◽  
Wenmin Zhang ◽  
Xiaodan Yang ◽  
Guo An ◽  
Wei Zhao
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Self Renewal

BACKGROUND: The voltage-gated calcium channel subunit alpha 2 delta 1 (α2δ1) is a functional tumor initial cells (TICs) marker for some solid cancer cells. This study aimed to investigate whether α2δ1 can be used as a potential TIC marker for breast cancer cells. METHODS: α2δ1+ and α2δ1- cells were identified and sorted from the breast cancer cell lines MDA-MB-231, MDA-MB-435s and ZR-75-1 by Immunofluorescence (IF) and Fluorescent-activated cell sorting (FACS) analyses. Spheroid formation in vitro and tumorigenesis in NOD/SCID mice were assessed to determine the self-renewal and serial transplantation abilities of these cells. Using a lentivirus infection system for α2δ1 in breast cancer cell lines, we determined the mRNA levels of stemnessassociated genes by quality real-time PCR (qRT-PCR). Boyden chamber and wounding assays were further performed to detect the migration of α2δ1 overexpression cells. Bioinformatics explored the relationship of molecular classification of breast cancer and drug resistance. RESULTS: α2δ1 presents on the cytomembrane of breast cancer cells, with a positive rate of 1.5–3%. The α2δ1+ cells in breast cancer cell lines have a stronger self-renewal ability and tumor initiating properties in vitro and in vivo. Overexpressing α2δ1 successfully enhanced the sphere-forming efficiency, and upregulated the expression of stemness-associated genes, and increased cell migration. However, seldom significant was available between estrogen receptor +/- (ER+/-), progesterone receptor (PR+/-), and Her2+/-. CONCLUSIONS: Breast cancer cells positive for the α2δ1 charactered tumor initiation, and α2δ1 is a potential TIC marker for breast cancer that further promotes the migration.

In vitro antiproliferative and apoptosis-inducing properties of a mononuclear copper(II) complex with dppz ligand, in two genotypically different breast cancer cell lines

BioMetals ◽  
2015 ◽  
Vol 28 (5) ◽  
pp. 929-943 ◽  
Author(s):  
Rajakumar Dhivya ◽  
Paramasivam Jaividhya ◽  
Anvarbatcha Riyasdeen ◽  
Mallayan Palaniandavar ◽  
Ganeshan Mathan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines
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