Salinomycin co-treatment enhances tamoxifen cytotoxicity in luminal A breast tumor cells by facilitating lysosomal degradation of receptor tyrosine kinases

Sommer, Ann‐Katrin; Hermawan, Adam; Mickler, Frauke Martina; Ljepoja, Bojan; Knyazev, Pjotr; Bräuchle, Christoph; Ullrich, Axel; Wagner, Ernst; Roidl, Andreas

doi:10.18632/oncotarget.10459

Cited by 18 publications

(15 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…that salinomycin potentiated cytotoxicity effect of tamoxifen by increasing caspase 3/7 activation in MCF‐7 cells. Moreover, our finding also are consistent with Sommer et al . which indicated the combination of salinomycin increased tamoxifen sensitivity in MCF‐7 cells via assisting lysosomal degradation of tyrosine kinase receptors.…”

Section: Discussionsupporting

confidence: 92%

Salinomycin overcomes acquired tamoxifen resistance through AIB1 and inhibits cancer cell invasion in endocrine resistant breast cancer

Manmuan

Sakunrangsit

Ketchart

2017

Clin Exp Pharma Physio

View full text Add to dashboard Cite

Salinomycin is a monocarboxylic polyether ionophore isolated from Streptomyces albus. It has been widely used as an antibiotic in veterinary medicine in poultry. A recent study demonstrated that salinomycin selectively inhibits human breast cancer stem cells; one possible mechanism of tamoxifen resistance. Our results show that salinomycin is effective in inhibiting MCF-7/LCC2 and MCF-7/LCC9 cell lines which are well-established endocrine resistant cells and has a synergistic effect in combination with tamoxifen using MTT proliferation assay. The inhibitory effect of salinomycin on the reduction of critical ER co-activator; amplified breast 1 (AIB1) mRNA and protein expression is overcoming tamoxifen resistance. Moreover, salinomycin significantly inhibits cell invasion in Matrigel invasion assay. The effect was mediated at least in part by the decrease of matrix metalopeptidase 9 (MMP-9) which is one critical enzyme facilitated in the cell invasion process. In conclusion, salinomycin should be developed as a novel agent used alone or in combination for endocrine-resistant breast cancer.

show abstract

Section: Discussionsupporting

confidence: 92%

Salinomycin overcomes acquired tamoxifen resistance through AIB1 and inhibits cancer cell invasion in endocrine resistant breast cancer

Manmuan

Sakunrangsit

Ketchart

2017

Clin Exp Pharma Physio

View full text Add to dashboard Cite

show abstract

“…SAL has been shown to inhibit CSCs in various cancer types; several studies have indicated that SAL combined with chemotherapeutic drugs, such as doxorubicin, tamoxifen, and cisplatin, enables synergistic anticancer activity in gastric cancer, breast cancer, and cholangiocarcinoma. 39 – 41 However, SAL possesses poor aqueous solubility and unfavorable properties in terms of toxicity. Thus, to overcome these disadvantages, nanoparticles have been used to deliver SAL.…”

Section: Discussionmentioning

confidence: 99%

<p>Salinomycin-Loaded Small-Molecule Nanoprodrugs Enhance Anticancer Activity in Hepatocellular Carcinoma</p>

Wang¹,

Zhuo²,

Tao³

et al. 2020

IJN

View full text Add to dashboard Cite

Background There is currently no effective treatment for advanced hepatocellular carcinoma (HCC), and chemotherapy has little effect on long-term survival of HCC patients, largely due to the cancer stem cell (CSC) chemoresistance of HCC. Methods We constructed a small-molecule nanometer-sized prodrug (nanoprodrug) loaded with salinomycin (SAL) for the treatment of HCC. SAL was encapsulated by the prodrug LA-SN38 (linoleic acid modified 7-ethyl-10-hydroxycamptothecin) to construct a self-assembled nanoprodrug further PEGylated with DSPE-PEG 2000 . We characterized this codelivered nanoprodrug and its antitumor activity both in vitro in human HCC cell lines and in vivo in mice. Results Delivery of the SAL- and LA-SN38-based nanoprodrugs effectively promoted apoptosis of HCC cells, exerted inhibition of HCC tumor-sphere formation as well as HCC cell motility and invasion, and reduced the proportion of CD133+ HCC-CSC cells. In nude mice, the nanoprodrug suppressed growth of tumor xenografts derived from human cell lines and patient. Conclusion Our results show that SAL-based nanoprodrugs are a promising platform for treating patients with HCC and a novel strategy for combination therapy of cancers.

show abstract

“…One such mechanism is intrinsic drug resistance; this means that tumor cells are resistant to the applied drug from the beginning of treatment. The other mechanism is acquired resistance, wherein tumor cells develop resistance to the applied drug following an initial response ( 50 ). In the present study, it was observed that in MEA A, for example, five times-treated cells exhibited the same sensitivity to DXR as untreated cells.…”

Section: Discussionmentioning

confidence: 99%

A proteomic analysis of chemoresistance development via sequential treatment with doxorubicin reveals novel players in MCF‑7 breast cancer cells

et al. 2018

Self Cite

View full text Add to dashboard Cite

Breast cancer exhibits the highest incidence of all cancer types and is the 2nd leading cause of cancer mortality in women. Up to 82% of breast cancer patients receive a chemotherapy-containing treatment regimen. However, numerous breast tumors recur within 10 years following an initial response and are frequently resistant to previous therapeutic agents. Thus, to analyze the crucial factors, and whether the development of resistance in tumor cells follows certain patterns, is of great importance. In the present study, the clinical treatment schedule of the frequently used chemotherapeutic drug doxorubicin was applied in an in vitro model, the Molecular Evolution Assay (MEA), leading to resistance formation. By investigating the alterations in protein expression in MCF-7 breast cancer cells with three biological replicates, it was observed that the development of resistance to doxorubicin is a multi-directed process. The number and composition of the differentially expressed proteins varied, in addition to the pathways involved in chemoresistance, leading to only a small number of proteins and pathways being commonly regulated in all the MEAs. The proteins 60S ribosomal export protein NMD3 and 4F2 cell-surface antigen heavy chain (SLC3A2) were identified to be the most promising differentially expressed targets; the gene ontology term 'apoptotic signaling pathway' was reduced and 'cell redox homeostasis' was upregulated. Based on the present findings in vitro, it may be hypothesized that the development of resistance in patients is an even more complex process, emphasizing the need for further investigations of resistance development in the clinic to eventually improve patient outcomes.

show abstract

Salinomycin co-treatment enhances tamoxifen cytotoxicity in luminal A breast tumor cells by facilitating lysosomal degradation of receptor tyrosine kinases

Cited by 18 publications

References 35 publications

Salinomycin overcomes acquired tamoxifen resistance through AIB1 and inhibits cancer cell invasion in endocrine resistant breast cancer

Salinomycin overcomes acquired tamoxifen resistance through AIB1 and inhibits cancer cell invasion in endocrine resistant breast cancer

<p>Salinomycin-Loaded Small-Molecule Nanoprodrugs Enhance Anticancer Activity in Hepatocellular Carcinoma</p>

A proteomic analysis of chemoresistance development via sequential treatment with doxorubicin reveals novel players in MCF‑7 breast cancer cells

Contact Info

Product

Resources

About