scholarly journals In Vitro Cytotoxicity of Trastuzumab (Tz) and Se-Trastuzumab (Se-Tz) against the Her/2 Breast Cancer Cell Lines JIMT-1 and BT-474

2021 ◽  
Vol 22 (9) ◽  
pp. 4655
Author(s):  
Priyanka Bapat ◽  
Debalina Goswami Sewell ◽  
Mallory Boylan ◽  
Arun K. Sharma ◽  
Julian E. Spallholz
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Sodium Selenite ◽  
In Vitro Cytotoxicity ◽  
Breast Cancer Cell Lines ◽  
Redox Cycle ◽  
Enzymatic Assays ◽  
Her 2 ◽  
Covalently Linked

Her/2+ breast cancer accounts for ~25% mortality in women and overexpression of Her/2 leads to cell growth and tumor progression. Trastuzumab (Tz) with Taxane is the preferred treatment for Her/2+ patients. However, Tz responsive patients often develop resistance to Tz treatment. Herein, redox selenides (RSe-) were covalently linked to Tz using a selenium (Se)-modified Bolton–Hunter Reagent forming Seleno-Trastuzumab (Se-Tz; ~25 µgSe/mg). Se-Tz was compared to Tz and sodium selenite to assess the viability of JIMT-1 and BT-474 cells. Comparative cell viability was examined by microscopy and assessed by fluorometric/enzymatic assays. Se-Tz and selenite redox cycle producing superoxide (O2•−) are more cytotoxic to Tz resistant JIMT-1 and Tz sensitive BT-474 cells than Tz. The results of conjugating redox selenides to Tz suggest a wider application of this technology to other antibodies and targeting molecules.

scholarly journals The Potential Utility of Curcumin in the Treatment of HER-2-Overexpressed Breast Cancer: AnIn VitroandIn VivoComparison Study with Herceptin

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Hung-Wen Lai ◽  
Su-Yu Chien ◽  
Shou-Jen Kuo ◽  
Ling-Ming Tseng ◽  
Hui-Yi Lin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signal Transduction ◽  
Cell Growth ◽  
Xenograft Model ◽  
Breast Cancer Cell Lines ◽  
Breast Cancers ◽  
Her 2 ◽  
Mcf 7

HER-2 is an important oncoprotein overexpressed in about 15–25% of breast cancers. We hypothesized that the ability of curcumin to downregulate HER-2 oncoprotein and inhibit the signal transduction pathway of PI3K/Akt, MAPK, and NF-κB activation may be important in the treatment of HER-2-overexpressed breast cancer. To examine the effect of curcumin on breast cancer cells, MCF-7, MDA-MB-231, MCF-10A, BT-474, and SK-BR-3-hr (a herceptin resistant strain from SK-BR-3) cells were used forin vitroanalysis. Thein vivoeffect of curcumin on HER-2-overexpressed breast cancer was investigated with the HER-2-overexpressed BT-474 xenograft model. Cell growth, cell cycle change, the antimobility effect, signal transduction, and xenograft volume analysis between groups treated with herceptin and/or curcumin were tested. Curcumin decreased the cell growth of various breast cancer cell lines (MCF-7, MDA-MB-231, MCF-10A, BT-474, and SK-BR-3-hr). In Western blot analysis, the phosphorylation of Akt, MAPK, and expression of NF-κB were reduced in BT-474 cells, but not in SK-BR-3-hr cells, after treatment with herceptin. When treated with curcumin, the HER-2 oncoprotein, phosphorylation of Akt, MAPK and expression of NF-κB were decreased in both BT-474 and SK-BR-3-hr cells. In the BT-474 xenograft model, though not as much as herceptin, curcumin did effectively decrease the tumor size. The combination of curcumin with herceptin was not better than herceptin alone; however, the combination of taxol and curcumin had an antitumor effect comparable with taxol and herceptin. The results suggested that curcumin has potential as a treatment for HER-2-overexpressed breast cancer.

Trastuzumab-HER/2 binding induced inhibition of cell growth and HER/2 tyrosine kinase activity

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21146-21146
Author(s):  
S. Welt ◽  
T. Shay ◽  
C. Lanning ◽  
K. Horton ◽  
D. Kostyal
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Tyrosine Kinase ◽  
Cell Lines ◽  
Fetal Calf Serum ◽  
Calf Serum ◽  
Breast Cancer Cell Lines ◽  
Inhibitory Effects ◽  
Her 2 ◽  
Post Menopausal

21146 Background: Cell lines containing the HER/2 amplicon are sensitive to Trastuzumab (T) mediated inhibition of cell growth. T blockade of cell growth signaling pathways have been hypothesized to occur by two mechanisms, inhibition of homo and hetro-dimerization of HER/2 with members of the EGFr family and inhibition of HER/2 phosphorylation. Methods: BT 474 and SK-BR3 breast cancer cell lines containing the HER/2 amplicon were cultured under condition demonstrating inhibitory effects of T by MTT and 3H-Thymidine incorporation (0.25–50 micrograms/ml for up to 9 days). RNA extracts from treated and un-treated cells were analyzed and compared using two immunoassays for phosphorylated HER/2. Various growth conditions were assessed for T inhibition of phosphorylation including, serum free media, fetal calf serum, human pre and post menopausal serum, breast cancer patient's serum and normal male serum. Results: Breast cancer cell lines BT 474 and SK-BR3 both demonstrated cell growth inhibition when cultured with T over a wide range of concentrations down to 0.25 microgram/ml. The inhibitory effects on SK-BR3 were low but statistically significant in both MTT and 3H-Thymidine incorporation assays. Examining this same concentration range of T on these cell lines demonstrated no appreciable reduction of phosphorylation by western blot analysis at various time points after exposure to T. Two different immune assays for HER/2 phosphorylation were analyzed. Further examination of replacement of fetal calf serum by human female pre and post menopausal serum samples or similar samples from breast cancer patients did not result in reduction of the phosphorylation signal. Conclusions: In this in vitro model T does not mediate effects through HER/2 tyrosine kinase inhibition under conditions that simulate clinical conditions. Whether inhibition of phosphorylation will be apparent at later time points is unknown. These finding may explain the activity of lapatinib, a HER/2 tyrosine kinase inhibitor, on T resistant breast cancer. No significant financial relationships to disclose.

scholarly journals In vitro Cytotoxicity Activity of Chrysin, Morin and Resveratrol Against MCF-7 Breast Cancer Cell Lines

2016 ◽  
Vol 13 (3) ◽  
pp. 1633-1637 ◽  
Author(s):  
Arlene Thomas ◽  
Niraja Ranadive ◽  
Harisha Nayak ◽  
Sneha Surendran ◽  
Madhavan Nampoothiri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
In Vitro Cytotoxicity ◽  
Breast Cancer Cell Lines ◽  
Cytotoxicity Activity ◽  
Mcf 7

Synthesis, Characterization, Molecular Docking, In Vitro Biological Evaluation and In Vitro Cytotoxicity Study of Novel Thiazolidine-4-One Derivatives as Anti-Breast Cancer Agents‏‏

2021 ◽  
Vol 21 ◽  
Author(s):  
Zainab Y. Kadhim ◽  
Hasanain G.J. Alqaraghuli ◽  
Muna Tawfeeq Abd
Keyword(s):  
Breast Cancer ◽  
Antibacterial Activity ◽  
Molecular Docking ◽  
Cell Growth ◽  
Breast Cancer Cells ◽  
Docking Study ◽  
In Vitro Cytotoxicity ◽  
T1 And T2 ◽  
Mcf 7

Background: Thiazolidine-4-one is a promising class of heterocyclic compounds with interesting pharmacological and biological activities, such as anticancer and antibacterial. Therefore, many researchers have synthesized thiazolidine-4-ones and evaluated their biological potential for developing new drugs. Objective: In this study, two novel thiazolidine-4-one derivatives (T1 and T2) were synthesized and evaluated for their antibacterial activity toward Staphylococcus aureus, Escherichia coli and Proteus mirabilis. Also, the cytotoxic activities of compounds T1 and T2 were estimated against MCF-7 (HER2+, ER+ and ER+) and MDA-MB-231 (triple-negative) human breast cancer cell lines. The chemical structure of compounds T1 and T2 was proven using spectral techniques (FT-IR, 1HNMR, and 13C-NMR) and CHN elemental analysis. Methods: The synthesis of thiazolidine-4-one compounds was performed in two steps. The first step consisted of the formation of Schiff bases S1 and S2. In the second step, the synthesized Schiff bases were reacted with thioglycolic acid to prepared thiazolidine-4-one compounds T1 and T2. Hemolysis assay, molecular docking, cytotoxicity activity (MTT assay) and antibacterial activity (disc diffusion assay) were studied. Results: The hemolysis study demonstrated that the hemolytic ratio of compounds T1 and T2 at (1, 2 and 3) mg/ml was less than 4%. MTT assay showed that 100 µg/ml of compounds T1 and T2 diminish the MCF-7 cell growth up to 80.05 ± 1.72 and 69.85 ± 3.26 respectively after 72 hrs, while the same concentration of compounds T1 and T2 reduces the MDA-MB-231 cell growth up 70.28 ± 2.31 and 57.15 ± 1.49, respectively. The inhibition zone of compounds T1 and T2 were 12 mm at 50 mg/ml and 10 mm at 5 mg/ml in E. coli bacteria. Furthermore, a docking study was carried out to investigate the affinity and binding mode of compounds T1 and T2 towards the ERα, VEGF, and HER2 protein receptors in breast cancer cells. Data obtained from the docking study were exactly identical to that obtained from in vitro cytotoxicity assay. Conclusion: The results proved that compound T1 is an optimal anticancer agent toward breast cancer cells and the hemolysis study indicates the use of safety inside the body for compound T1. Synthesized compound T1 was most effective against MCF-7 cells compared to MDA-MB-231 cells and more effective than the reference drug tamoxifen in breast cell lines. The high cytotoxicity of compound T1 on the growth of MCF‐7 cells because T1 binds with a high degree of affinity to the estrogen and HER2 receptors, which in turn inhibits cell proliferation and induces apoptosis.

scholarly journals Verteporfin Inhibits Cell Proliferation and Induces Apoptosis in Different Subtypes of Breast Cancer Cell Lines Without Light Activation

2020 ◽  
Author(s):  
Changran Wei ◽  
Xiangqi Li
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Hippo Pathway ◽  
Breast Cancer Cell Lines ◽  
Hippo Signaling ◽  
Luminal A ◽  
Ki 67 ◽  
Her 2

Abstract Background Breast cancer (BC) can be separated into four molecular subclassifications including Lumina1 A, Lumina1 B, HER-2 overexpression and Basal-like subtype. These classifications are based on estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2) and cell proliferation antigen (Ki-67). The Hippo signaling pathway plays an indispensable role in BC. The YAP1 gene is a terminal effector of Hippo pathway, and hyperactivation of YAP mediates tumorigenesis. As an inhibitor of YAP, non-photoactivated verteporfin (VP) can inhibit YAP-mediated tumor proliferation and angiogenesis by eliminating its interaction with TEAD. This study set out to determine the effect and molecular mechanisms of VP-mediated inhibition of YAP in different subtypes of BC. Methods Luminal A, Luminal B and Basal-like BC cells were cultivated in vitro in order to study effect of VP on proliferation and apoptosis on these three molecular BC subtypes. Results Our experimental results show that VP inhibits cell proliferation, YAP-TEAD interaction and its downstream target expression. VP also induces tumor cell apoptosis, and promotes the cleavage of Caspase-9 and PARP in various molecular subtypes of BC cells. Conclusion These findings provide a basis for VP as a potential anti-tumor therapeutic for BC by targeting the Hippo pathway effector YAP.

Selective inhibition of ADAM metalloproteases blocks HER-2 extracellular domain (ECD) cleavage and potentiates the anti-tumor effects of trastuzumab

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13021-13021 ◽  
Author(s):  
P. Scherle ◽  
X. Liu ◽  
J. Li ◽  
J. Fridman ◽  
Y. Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase I ◽  
Cancer Patients ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Therapeutic Intervention ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Her 2

13021 Background: HER-2, a member of ErbB family of receptor tyrosine kinases, is an important regulator of cell proliferation and survival, and is a clinically validated target of therapeutic intervention in HER-2 positive metastatic breast cancer patients. In HER-2 overexpressing cells, the extracellular domain (ECD) is frequently cleaved, rendering the remaining transmembrane portion of HER-2 (p95) constitutively active. The presence of both serum ECD and cellular p95 protein have been linked to poor clinical outcome as well as reduced effectiveness of some therapeutic treatments, suggesting that signaling via p95 is clinically relevant and may represent an attractive target for therapeutic intervention. Methods: Through medicinal chemistry efforts, we have identified a series of potent, selective small molecule inhibitors of ADAM metalloproteases, exemplified here by INCB7839. These compounds were tested both in vitro and in vivo for inhibition of HER-2 ECD cleavage and anti-tumor activity in the HER-2 overexpressing BT-474 cell line. Inhibition of circulating HER-2 ECD levels was monitored in a phase I multiple dose escalation study in healthy volunteers. Results: We demonstrate that these inhibitors effectively blocked HER-2 cleavage in HER-2 overexpressing human breast cancer cell lines. When used in combination, INCB7839 dramatically enhanced the antiproliferative activity of suboptimal doses of the anti-HER-2 antibody, trastuzumab, in HER-2 overexpressing/shedding breast cancer cell lines, accompanied by reduced ERK and AKT phosphorylation. Consistent with these in vitro data, INCB7839 reduced serum ECD levels in tumor-bearing mice and enhanced the antitumor effect of trastuzumab in a xenograft tumor model derived from the HER-2 overexpressing BT-474 breast cancer cell line. In a phase I clinical trial, INCB7839 demonstrated a dose-dependent decrease in the circulating levels of HER-2 ECD present in healthy volunteers. Conclusions: Collectively, these findings suggest that blocking HER-2 cleavage with selective ADAM inhibitors, especially in combination with anti-HER-2 antibody therapy, may represent a novel approach for treating HER-2 overexpressing breast cancer patients. [Table: see text]

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