ChemInform Abstract: Antitumor Benzothiazoles. Part 3. Synthesis of 2-(4-Aminophenyl) benzothiazoles and Evaluation of Their Activities Against Breast Cancer Cell Lines in vitro and in vivo.

ChemInform ◽  
2010 ◽  
Vol 27 (49) ◽  
pp. no-no
Author(s):  
D.-F. SHI ◽  
T. D. BRADSHAW ◽  
S. WRIGLEY ◽  
C. J. MCCALL ◽  
P. LELIEVELD ◽  
...  

2011 ◽  
Vol 63 (2) ◽  
pp. 264-271 ◽  
Author(s):  
Gopal Singh ◽  
Argun Akcakanat ◽  
Chandeshwar Sharma ◽  
David Luyimbazi ◽  
Katherine Naff ◽  
...  


2021 ◽  
Author(s):  
Saima Najm ◽  
Humaira Naureen ◽  
Fareeha Anwar ◽  
Muhammad Mubbashir Khan ◽  
Rabia Ali

Abstract Background and objectives: Breast cancer presents high morbidity among women with various treatment challenges. This study aims to evaluate the repurposed lamotrigine schiff base metal (LTG-SB-M) coordinates against in-vitro MCF-7 breast cancer cell lines and in-vivo N-methylnitrosourea (NMU)-persuaded toxicity of rats’ mammary gland. Method: In-silico computational analysis and in vitro cytotoxic studies on MCF-7 breast cancer cell lines was executed to build up the assumptions. In-vivo NMU-induced anticancer potential was assessed in forty Wistar rats; assigned into five groups of 8 rats each. Group I served as normal control and received normal saline, Group II received NMU (50 mg/kg), Group III received tamoxifen, whereas; Group IV and V received LTG-SB-M derivative (LAC3, LBC3) at dose of 100 mg/kg body weight, for 15 consecutive days. Intraperitoneal injection of NMU (single dose) was given at the age of 5, 9 and 13 weeks to the rats with the three week interval. For all experimental animals; biochemical markers were assessed. DNA strand breakage alongside the hormonal profile of estrogen and progesterone was also estimated. Results: All tested compounds present significant activity against MCF-7 cell lines in vitro and NMU-induced mammary tumor in vivo. The in vivo results of tested compounds present a significant decrease in weight of organ; with reinstated renal and hepatic enzymes. Histological analysis revealed strong countenance of proteins, estrogen, and progesterone in NMU-treated rats. Conclusion: These results suggest that LTG-SB-M complex can be used as better anticancer agent against breast cancer.



2011 ◽  
Vol 17 (16) ◽  
pp. 5275-5286 ◽  
Author(s):  
Rachel Sharpe ◽  
Alex Pearson ◽  
Maria T. Herrera-Abreu ◽  
Damian Johnson ◽  
Alan Mackay ◽  
...  


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13070-13070 ◽  
Author(s):  
W. Miao ◽  
M. Loignon ◽  
L. Hu ◽  
M. Basik ◽  
G. Batist

13070 Background: Nrf2 is a master transcription factor regulating multiple phase II carcinogen-detoxifying enzymes. Modulating Nrf2 is a current chemoprevention strategy under investigation. Nrf2 levels are regulated by the Keap1, which functions as a substrate adaptor protein targeting Nrf2 to the Cullin-3 (Cul3)-dependent ubiquitin E3 ligase complex. Methods: We used RT-PCR and Western blot to measure the mRNA and protein levels of Nrf2, Keap1 and Cul3 in human breast cancer cell lines. SiRNA and retrovectors were used to construct stable Cul3 silenced breast cancer cell lines. Agilent DNA microarray analysis was used to study the Cul3-slienced cells. Results: We discovered that Nrf2 protein levels in both nucleus and cytoplasm are significantly decreased in all breast cancer cell lines examined compared to normal human mammary epithelial cells (HMEC). This was confirmed with IHC analysis in 8 out of 10 breast cancer specimens containing normal mammary tissues for comparison. Since RT-PCR showed no change in Nrf2 mRNA levels in the breast cancer cell lines, we examined the degradation pathway of Nrf2, and we found that Cul3 is significantly overexpressed in all three breast cancer cell lines studied compared to HMEC. Silencing Cul3 using siRNA results in restoration of Nrf2 protein level, along with multiple carcinogen-detoxifying enzymes, such as GCS. The Cul3 silenced cells showed remarkable growth retardation compared to the wild type MCF-7 cell line both in vitro and in vivo in a mouse mammary fat pad cancer xenograft model. Microarray analyses of Cul3 siRNA-slinced cells demonstrated upregulation of several detoxifying genes, altered cell cycle markers and several upregulated tumor suppressor genes. Conclusions: Nrf2 is significantly downregulated in breast cancer cells, which is related to the overexpression of Cul3, and may represent sensitivity of these cells to carcinogenic transformation. Knocking down Cul3 constitutively upregulates the Nrf2 as well as multiple carcinogen-detoxifying genes. Moreover, it significantly suppressess the proliferation of cancer cells in vitro and growth of xenograft tumors in vivo. These data suggest that Cul-3 is a potential new target for breast cancer chemoprevention and treatment. No significant financial relationships to disclose.



2014 ◽  
Vol 13 (6) ◽  
pp. 1419-1430 ◽  
Author(s):  
Lynn Y.L. Huang ◽  
Chia-Chi Chang ◽  
Ying-Shuan Lee ◽  
Jia-Ming Chang ◽  
Jiann-Jyh Huang ◽  
...  


2017 ◽  
Vol 63 (1) ◽  
pp. 141-145
Author(s):  
Yuliya Khochenkova ◽  
Eliso Solomko ◽  
Oksana Ryabaya ◽  
Yevgeniya Stepanova ◽  
Dmitriy Khochenkov

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



2019 ◽  
Vol 15 (7) ◽  
pp. 738-742 ◽  
Author(s):  
Adnan Badran ◽  
Atia-tul-Wahab ◽  
Sharmeen Fayyaz ◽  
Elias Baydoun ◽  
Muhammad Iqbal Choudhary

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.



2021 ◽  
pp. 1-11
Author(s):  
Meng Li ◽  
Wenmin Zhang ◽  
Xiaodan Yang ◽  
Guo An ◽  
Wei Zhao

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.



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