A novel small molecule inhibitor of CD151 inhibits proliferation of metastatic triple negative breast cancer cell lines

Gavara, Murali Mohan; Zaveri, Kunal; Badana, Anil Kumar; Gugalavath, Shailender; Amajala, Krishna Chaitanya; Patnala, Kiranmayi; Malla, Rama Rao

doi:10.1016/j.procbio.2017.12.004

Cited by 12 publications

(4 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Co-immunoprecipitation assays suggest that CD151 interacts with viral NP, M1, and NEP proteins ( 102 ); however, the exact domains involved in interaction and the mechanism of CD151 function in nuclear export remain unclear. Given that a small molecule inhibitor for CD151 is now under development ( 103 ), more data revealing the role of CD151 in IAV infection and subsequent use in targeting CD151 as anti-IAV therapy is anticipated.…”

Section: Strategies Targeting Host Cell Machinerymentioning

confidence: 99%

Advancements in Host-Based Interventions for Influenza Treatment

et al. 2018

View full text Add to dashboard Cite

Influenza is a major acute respiratory infection that causes mortality and morbidity worldwide. Two classes of conventional antivirals, M2 ion channel blockers and neuraminidase inhibitors, are mainstays in managing influenza disease to lessen symptoms while minimizing hospitalization and death in patients with severe influenza. However, the development of viral resistance to both drug classes has become a major public health concern. Vaccines are prophylaxis mainstays but are limited in efficacy due to the difficulty in matching predicted dominant viral strains to circulating strains. As such, other potential interventions are being explored. Since viruses rely on host cellular functions to replicate, recent therapeutic developments focus on targeting host factors involved in virus replication. Besides controlling virus replication, potential targets for drug development include controlling virus-induced host immune responses such as the recently suggested involvement of innate lymphoid cells and NADPH oxidases in influenza virus pathogenesis and immune cell metabolism. In this review, we will discuss the advancements in novel host-based interventions for treating influenza disease.

show abstract

Section: Strategies Targeting Host Cell Machinerymentioning

confidence: 99%

Advancements in Host-Based Interventions for Influenza Treatment

et al. 2018

View full text Add to dashboard Cite

show abstract

“…The nucleotide analog TAU reduced the proliferation of TNBC cells as well as CD151 expression. 11 The cell-line growth curves were usually applied for the determination of population doubling time, maximum growth rate, and best time range for evaluating the effect of drugs. The cells were treated with TAU (10-50nM) for 24h and IC50 value was Supplementary Figure 1.…”

Section: Effect Of Tau and Ptx On The Viability Of Ptxr/tnbc Cellsmentioning

confidence: 99%

“…As TAU targets CD151 in TNBC cells, 11 and drugresistant proteins in PTX resistant TNBC cells, the possible role of CD151 in drug resistance was further explored. For this study, CD151 was overexpressed in PTX resistant TNBC cell types, and the expression of ABC transporters was determined by western blot analysis.…”

Section: Effects Of Tau and Ptx Drug Resistance Mechanism Of Ptxr/tnb...mentioning

confidence: 99%

“…9,10 TAU also targeted CD151 and inhibited the viability of the MDA-MB-231 cells. 11 Therefore, the development of novel combinations containing PTX with targeted therapeutics to combat drug-resistant TNBC is the focus of current research. This study is intended to establish the role of TAU in sensitizing PTX-resistant MDA-MB-231(mesenchymal stem-like; basal B) and -MDA-MB-468 (basal-like 1; basal A) TNBC cells.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Antiviral Drug 2-thio-6-azauridine Sensitizes Paclitaxel-Resistant Triple Negative Breast Cancer Cells by Targeting Mammosphere Formation and ABC Transporters

Malla

Marni

Gavara³

et al. 2022

Arch Breast Cancer

View full text Add to dashboard Cite

Background: 2-thio-6-azauridine (TAU) is a nucleoside analog and potential antiviral drug. The antiproliferative activity of TAU has been evaluated in limited cancer cell lines. The present study is aimed to evaluate the effect of TAU on drug sensitization mechanism in paclitaxel (PTX) resistant triple-negative breast cancer (TNBC) cells.Methods: The cell death mechanism was determined using MTT, BrdU incorporation, apoptosis, and DNA damage Western blot and RT-PCR assays. A specific ELISA method was used to determine the caspase-3 activity and expression levels of MRP1, MDR1, BCRP, and MRP8. Western blot analysis was used to assess the expression of CD151, MRP1, MDR1, and BCRP in CD151 overexpressing PTX-resistant TNBC cells.Results: The combination of TAU and PTX (10:20nM) synergistically inhibited the 50% viability of 12-fold PTX-resistant TNBC cells. Mechanistically, the combination inhibited the proliferation by arresting the cell cycle at the G2M phase and induced apoptosis by altering cell integrity and nuclear morphology as well as damaging DNA. The combination sensitized the PTX-resistant TNBC cells by increasing BAX and decreasing Bcl-2 expression, activating caspase-3, and reducing the expression of ABC transporters MRP1 and MDR1. The combination reduced the expression of MRP1 and MDR1 in CD151 overexpressing PTX-resistant TNBC cells, indicating the role of CD151in TAU mediated sensitization of PTX-resistant TNBC cells. The combination also reduced the mammosphere formation efficiency of PTX-resistant TNBC cells. Conclusion: Overall, the present study illustrated the promising ability of TAU in sensitizing drug-resistant TNBC cells to PTX.

show abstract

In silico study suggests potential drugs that target CD151 to treat breast cancer and glioblastoma

Ramírez‐Salinas,

Rosales‐Hernandéz,

Correa‐Basurto

et al. 2024

J Comput Chem

View full text Add to dashboard Cite

Recently tetraspanin CD151 has been identified as an important biological target involved in metastatic processes which include cell adhesion, tumor progression processes, and so forth in different types of cancers, such as breast cancer and glioblastoma. This in Silico study considered 1603 compounds from the Food and Drug Administration database, after performing an ADMET analysis; we selected 853 ligands, which were used for docking analysis. The most promising ligands were selected from docking studies, based on two criteria: (a) showed lowest affinity to the CD151 protein and (b) they interact with the QRD motif, located in the second extracellular loop. Furthermore, we investigate the stability of the protein‐ligand complexes through MD simulations as well as free energy MM‐PBSA calculations. From these results, loperamide and glipizide were identified as the best evaluated drugs. We suggest an in vitro analysis is needed to confirm our in silico prediction studies.

show abstract

A novel small molecule inhibitor of CD151 inhibits proliferation of metastatic triple negative breast cancer cell lines

Cited by 12 publications

References 53 publications

Advancements in Host-Based Interventions for Influenza Treatment

Advancements in Host-Based Interventions for Influenza Treatment

Antiviral Drug 2-thio-6-azauridine Sensitizes Paclitaxel-Resistant Triple Negative Breast Cancer Cells by Targeting Mammosphere Formation and ABC Transporters

In silico study suggests potential drugs that target CD151 to treat breast cancer and glioblastoma

Contact Info

Product

Resources

About