scholarly journals Antidepressant Sertraline Hydrochloride Inhibits the Growth of HER2+ AU565 Breast Cancer Cell Line through Induction of Apoptosis, and Arrest of Cell Cycle

2021 ◽  
Author(s):  
Atia-tul- Wahab ◽  
Sharmeen Fayyaz ◽  
Rimsha Irshad ◽  
Rafat A. Siddiqui ◽  
Atta-ur- Rahman ◽  
...  

AbstractBreast cancer is one the most aggressive cancer worldwide, especially Pakistan due to limited therapeutic options. This study was conducted to repurpose the use of selective serotonin reuptake inhibitors (SSRIs), in the treatment of breast cancers, and merit to pursue drug re-positioning in oncology. Anti-proliferative activity of SSRIs, such as fluoxetine, paroxetine, and sertraline hydrochloride on the growth of AU-565, MCF-7, MDA-MB-231, and BT-474 breast cancer cell lines, along with human fibroblast BJ cells was determined in vitro. Changes in nuclear morphology (DAPI staining), and induction of apoptosis (flow cytometry, and caspase-3 activation) were also studied. Sertraline hydrochloride most effectively inhibited the growth of breast cancer cells in vitro. Therefore, pharmacological mechanism involved in sertraline mediated cell death was investigated in HER2+ AU565 cell line. Enhanced nuclear fragmentation, increased Annexin (+) cells, and caspase-3/7 activation indicated that sertraline-mediated cell death could be a result of BCl2-independent apoptosis as evidenced by expression of Bax, and BCl2 genes. Taken together, our results identified sertraline hydrochloride, as a potential candidate for the treatment of HER2-positive breast cancer. Even though these are in vitro results, this study opens great opportunity in the field of drug repurposing for the development of chemotherapeutic agents.

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


Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3281
Author(s):  
Syed Sarim Imam ◽  
Sultan Alshehri ◽  
Mohammad A. Altamimi ◽  
Afzal Hussain ◽  
Wajhul Qamar ◽  
...  

The present research work is designed to prepare and evaluate piperine liposomes and piperine–chitosan-coated liposomes for oral delivery. Piperine (PPN) is a water-insoluble bioactive compound used for different diseases. The prepared formulations were evaluated for physicochemical study, mucoadhesive study, permeation study and in vitro cytotoxic study using the MCF7 breast cancer cell line. Piperine-loaded liposomes (PLF) were prepared by the thin-film evaporation method. The selected liposomes were coated with chitosan (PLFC) by electrostatic deposition to enhance the mucoadhesive property and in vitro therapeutic efficacy. Based on the findings of the study, the prepared PPN liposomes (PLF3) and chitosan coated PPN liposomes (PLF3C1) showed a nanometric size range of 165.7 ± 7.4 to 243.4 ± 7.5, a narrow polydispersity index (>0.3) and zeta potential (−7.1 to 29.8 mV). The average encapsulation efficiency was found to be between 60 and 80% for all prepared formulations. The drug release and permeation study profile showed biphasic release behavior and enhanced PPN permeation. The in vitro antioxidant study results showed a comparable antioxidant activity with pure PPN. The anticancer study depicted that the cell viability assay of tested PLF3C2 has significantly (p < 0.001)) reduced the IC50 when compared with pure PPN. The study revealed that oral chitosan-coated liposomes are a promising delivery system for the PPN and can increase the therapeutic efficacy against the breast cancer cell line.


2018 ◽  
Vol 7 (3) ◽  
pp. 424
Author(s):  
Yuastika Puspita Sari ◽  
Hirowati Ali ◽  
Aswiyanti Asri

Kanker payudara yang paling banyak ditemukan adalah subtipe luminal A dengan karakteristik Estrogen Reseptor+. Subjek penelitian akan diwakili oleh cell line MCF-7 dan Umbilical Cord Blood Mesenchymal Stem Cell (UCBMSC). Over expression Myc pada kanker payudara mengakibatkan sel kanker menjadi lebih invasif dan terjadi resistensi terhadap terapi hormonal. Tujuan penelitian ini adalah mengidentifikasi ekspresi gen Myc pada cell line MCF-7 sebelum dan sesudah pemberian sel punca. Penelitian ini menggunakan desain experimental secara in vitro. Sampel menggunakan MCF-7 dan sel punca yang dibagi menjadi 4 kelompok, yaitu K1 (kelompok kontrol MCF-7), K2 (kelompok kontrol sel punca), P1 (perlakuan subkultur MCF-7 dengan sel punca inkubasi 24 jam), dan P2 (inkubasi 48 jam). Kemudian, dilakukan isolasi RNA, sintesis cDNA, dan ekspresi Myc diperiksa menggunakan PCR dan elektroforesis. Analisa data yang digunakan adalan One Way ANOVA dan post-hoc LSD. Hasil analisis bivariat didapatkan p<0,05. Dari uji post-hoc LSD tidak ditemukan perbedaan yang bermakna antara K1 dengan P1, K1 dengan P2, dan K2 dengan P2. Namun, tetap ditemukan perbedaan yang bermakna antara K2 dengan P1 dan P1 dengan P2. Simpulan penelitian ini adalah tidak terdapat perbedaan bermakna ekspresi gen Myc pada subkultur antara MCF-7 breast cancer cell line dengan pemberian sel punca mesenkimal.


2014 ◽  
Vol 8 (Suppl 4) ◽  
pp. P22
Author(s):  
Klesia Madeira ◽  
Murilo Cerri ◽  
Renata Daltoé ◽  
Alice Herlinger ◽  
João Filho ◽  
...  

2000 ◽  
Vol 68 (4) ◽  
pp. 369-377 ◽  
Author(s):  
S.N. Pandeya ◽  
P. Yogeeswari ◽  
E.A. Sausville ◽  
A.B. Mauger ◽  
V.L. Narayanan

Various 4-substituted phenyl semicarbazone derivatives were synthesized and evaluated in vitro by NCI in the 3-cell line, one dose primary anticancer assay. Three compounds showed significant activity against breast MCF7 cell line and were further evaluated for potential anticancer activity in an in vitro human disease-oriented tumour cell line screening panel that consisted of 60 human tumour cell lines arranged in nine subpanels, representing diverse histologies. Leukemia, colon, ovarian and breast cancer cell lines were relatively more sensitive to these compounds than the other cell lines. The 4-carboxy substituted p-nitrobenzylidene phenyl semicarbazone (1c) emerged as the most active compound with average GI50 value (the molar drug concentration required for the 50% growth inhibition) of 28.6µM. This compound showed greater activity than methotrexate against NCI-H226(Lung), BT-549 and T-47D(Breast) cancer cell lines.


2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Thandi Mqoco ◽  
André Stander ◽  
Anna-Mart Engelbrecht ◽  
Anna M Joubert

Current chemotherapeutic agents have many side effects and are toxic to normal cells, providing impetus to identify agents that can effectively eliminate tumorigenic cells without damaging healthy cells. The aim of this study was to examine whether combining a novel BRD4 inhibitor, ITH-47, with the antimitotic estradiol analogue, ESE-15-ol, would have a synergistic effect on inhibiting the growth of two different breast cancer cell lines in vitro. Our docking and molecular dynamics studies showed that compared to JQ1, ITH-47 showed a similar binding mode with hydrogen bonds forming between the ligand nitrogens of the pyrazole, ASN99, and water of the BRD4 protein. Data from cell growth studies revealed that the GI50 of ITH-47 and ESE-15-ol after 48 hours of exposure was determined to be 15 μM and 70 nM, respectively, in metastatic MDA-MB-231 breast cancer cells. In tumorigenic MCF-7 breast cancer cells, the GI50 of ITH-47 and ESE-15-ol was 75 μM and 60 nM, respectively, after 48 hours of exposure. Furthermore, the combination of 7.5 μM and 14 nM of ITH-47 and ESE-15-ol, respectively, resulted in 50% growth inhibition of MDA-MB-231 cells resulting in a synergistic combination index (CI) of 0.7. Flow cytometry studies revealed that, compared to the control, combination-treated MDA-MB-231 cells had significantly more cells present in the sub-G1 phase and the combination treatment induced apoptosis in the MDA-MB-231 cells. Compared to vehicle-treated cells, the combination-treated cells showed decreased levels of the BRD4, as well as c-Myc protein after 48 hours of exposure. In combination, the selective BRD4 inhibitor, ITH-47, and ESE-15-ol synergistically inhibited the growth of MDA-MB-231 breast cancer cells, but not of the MCF-7 cell line. This study provides evidence that resistance to BRD4 inhibitors may be overcome by combining inhibitors with other compounds, which may have treatment potential for hormone-independent breast cancers.


2005 ◽  
Vol 12 (4) ◽  
pp. 839-850 ◽  
Author(s):  
P L Jeffery ◽  
R E Murray ◽  
A H Yeh ◽  
J F McNamara ◽  
R P Duncan ◽  
...  

While oestrogen, progesterone and growth factors, including growth hormone (GH), are clearly implicated in the pathogenesis of breast cancer, there is now evidence that the newly described ghrelin axis is also involved. The aims of this study were to investigate the expression of the ghrelin axis in breast cancer tissues and cell lines and to examine the effect of ghrelin on breast cancer cell proliferation in vitro. Ghrelin and its functional receptor, the growth hormone secretagogue receptor (GHSR) type 1a, were expressed in normal breast tissue and breast cancer specimens and cell lines. In contrast, the truncated GHSR type 1b isoform was exclusively expressed in breast carcinoma, suggesting that it has potential as a diagnostic marker. Ghrelin treatment significantly increases the proliferation of the MDA-MB-435 and MDA-MB-231 breast cancer cell lines in vitro. In addition, we have described the expression of a human preproghrelin isoform, exon 3-deleted preproghrelin, which encodes mature ghrelin plus a novel C-terminal peptide. Quantitative RT-PCR was used to demonstrate that this mRNA isoform is highly expressed in the MDA-MB-435 metastatic breast cancer cell line relative to the benign MCF-10A breast epithelial cell line. The unique C-terminal peptide of exon 3-deleted preproghrelin is expressed in the glandular epithelium of breast cancer tissues, with high-grade carcinoma exhibiting the strongest immunoreactivity. The data presented here suggest that components of the ghrelin axis may represent novel markers for breast cancer and potential therapeutic targets.


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