The novel toluidine sulphonamide EL102 shows pre-clinical in vitro and in vivo activity against prostate cancer and circumvents MDR1 resistance

Toner, Aidan; McLaughlin, Fiona; Giles, Frank; Sullivan, Frank; O’Connell, Enda; Carleton, Laura A.; Breen, Laura; Dunne, Gráinne; Gorman, Adrienne M.; Lewis, Joe; Glynn, Sharon A.

doi:10.1038/bjc.2013.537

Cited by 11 publications

(4 citation statements)

References 33 publications

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“…The present study supported the results published by Galal, Abdelaziz, Toner, and Liu [19,32,41,42]. It was reported that the synthesized compounds mediated their anticancer action through the binding to the colchicine-binding site of tubulin and exert part of their action through arresting cell division at the G2/M phase.…”

Section: Ic50supporting

confidence: 92%

Antiproliferative Evaluation and Molecular Docking studies of some Sulfonyl-α-L-amino acid Derivatives coupled with Anisamide Scaffold

Galal

Mahmoud

2021

Egypt. J. Chem.

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A series of sulfonyl-α-L-amino acid derivatives coupled with anisamide scaffold, previously synthesized, were evaluated in vitro for their antiproliferative activity against human cell lines namely, Caucasian breast adenocarcinoma (MCF7), hepatocellular carcinoma (HEPG2), Colon cell line (HCT116), and pancreatic cell line (PaCa2) and comparing their results with skin fibroblast cell line (BJ1) as a normal cell line, using MTT cell proliferation assay. The results showed that 2-(4-{[(5-Chloro-2-methoxy-benzoyl)amino]methyl}phenyl)sulfonyl-L-cysteine (5), 2-(4-{[(5-Chloro-2-methoxy-benzoyl)amino]methyl}phenyl)sulfonyl-L-glutamine ( 14), and 2-(4-{[(5-Chloro-2-methoxy-benzoyl)amino]methyl}phenyl)sulfonyl-L-tryptophan (18) were the most active molecules against HEPG2, MCF7, and PaCa2 cell lines with IC50 51.9, 54.2, and 59.7 µg/ml respectively. On contrary, 2-(4-{[(5-Chloro-2-methoxy-benzoyl)amino]methyl}phenyl)sulfonyl-L-valine (3) has a high selectivity index for (MCF7) and ( PaCa2) cell lines at, IC50 90.9 and 69.5 µg/ml, respectively. Similarly, 2-(4-{[(5-Chloro-2-methoxy-benzoyl)amino]methyl}phenyl)sulfonyl-L-glycine (1) and 2-(4-{[(5-Chloro-2-methoxy-benzoyl)amino]methyl}phenyl)sulfonyl-Llysine (10) have cytotoxic selectivity towards (HEPG2) cell line with a high selectivity index with IC50 85.1 and 87.0 µg/ml, respectively. Moreover, a docking study was performed to predict the correct binding geometry for each binder and compare it with its activity.

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Section: Ic50supporting

confidence: 92%

Antiproliferative Evaluation and Molecular Docking studies of some Sulfonyl-α-L-amino acid Derivatives coupled with Anisamide Scaffold

Galal

Mahmoud

2021

Egypt. J. Chem.

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“…The results demonstrated that Sorcin silencing increased the intracellular concentration of Rhod-123 and decreased the expression of P-gp to reverse the drug resistance of tumor cells. MDR1, LRP and MRP1 are the most common membrane transporters that efflux drugs out of cells and are frequently found to be overexpressed in the drug resistant environment (13)(14)(15). The expression of these proteins in A549/DDP cells prior to and following Sorcin silencing was investigated.…”

Section: Discussionmentioning

confidence: 99%

Reversing effect and mechanism of soluble resistance-related calcium-binding protein on multidrug resistance in human lung cancer A549/DDP cells

Gao

Liu

et al. 2014

Molecular Medicine Reports

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Abstract. Lung cancer is the primary malignancy of the lung and is the leading cause of cancer-associated mortality in China. Multidrug resistance (MDR) is an essential aspect of lung cancer treatment failure and a popular topic of investigation in tumor studies. Previous studies have demonstrated that soluble resistance-related calcium-binding protein (Sorcin) is involved in the MDR of various types of human tumor, and that silencing Sorcin was able to reverse the MDR of several types of cultured human cancer cells. However, the effect and potential mechanism underlying the ability of Sorcin to reverse MDR in human lung cancer remains to be fully elucidated. The present study examined the role of Sorcin in the reversal of MDR in human lung cancer A549/DDP cells. The effects included increased drug sensitivity to cisplatin, apoptotic rate, cell cycle arrest in the G2/M phase and intracellular accumulation of rhodamine-123, and decreased expression of multidrug resistance gene 1, lung resistance protein, multidrug resistance-associated protein, glutathione S-transferase π, ATP-binding cassette transporter A2 (ABCA2), ABCA5, B-cell lymphoma 2 and P-glycoprotein, and the depletion of glutathione in Sorcin-silenced A549/DDP cells. The present study also revealed that there was a downregulation of p-Akt and phosphorylated extracellular signal-regulated kinase (p-ERK), and a decreased transcriptional activation of nuclear factor κB, signal transducer and activator of transcription (STAT)3, STAT5 and nuclear factor of activated T-cells following silencing of Sorcin. The results indicated that Sorcin may be used as a potential therapeutic target for MDR through inhibiting the Akt and ERK pathways in human lung cancer.

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“…However, inhibiting MDR1 directly may not be the method to overcome drug efflux and resistance to taxanes. Despite positive in vitro and in vivo studies [ 163 , 306 , 319 , 320 , 321 ], clinically, MDR1 inhibitors have not been successful. This could be due to the increased toxicity of taxanes, increased levels of supplementary drug transporters, or upregulation of other resistance mechanisms.…”

Section: Taxane Resistance In Prostate Cancermentioning

confidence: 99%

Mechanisms of Taxane Resistance

Maloney

Hoover

Morejon-Lasso

et al. 2020

Cancers

121

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The taxane family of chemotherapy drugs has been used to treat a variety of mostly epithelial-derived tumors and remain the first-line treatment for some cancers. Despite the improved survival time and reduction of tumor size observed in some patients, many have no response to the drugs or develop resistance over time. Taxane resistance is multi-faceted and involves multiple pathways in proliferation, apoptosis, metabolism, and the transport of foreign substances. In this review, we dive deeper into hypothesized resistance mechanisms from research during the last decade, with a focus on the cancer types that use taxanes as first-line treatment but frequently develop resistance to them. Furthermore, we will discuss current clinical inhibitors and those yet to be approved that target key pathways or proteins and aim to reverse resistance in combination with taxanes or individually. Lastly, we will highlight taxane response biomarkers, specific genes with monitored expression and correlated with response to taxanes, mentioning those currently being used and those that should be adopted. The future directions of taxanes involve more personalized approaches to treatment by tailoring drug–inhibitor combinations or alternatives depending on levels of resistance biomarkers. We hope that this review will identify gaps in knowledge surrounding taxane resistance that future research or clinical trials can overcome.

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The novel toluidine sulphonamide EL102 shows pre-clinical in vitro and in vivo activity against prostate cancer and circumvents MDR1 resistance

Cited by 11 publications

References 33 publications

Antiproliferative Evaluation and Molecular Docking studies of some Sulfonyl-α-L-amino acid Derivatives coupled with Anisamide Scaffold

Antiproliferative Evaluation and Molecular Docking studies of some Sulfonyl-α-L-amino acid Derivatives coupled with Anisamide Scaffold

Reversing effect and mechanism of soluble resistance-related calcium-binding protein on multidrug resistance in human lung cancer A549/DDP cells

Mechanisms of Taxane Resistance

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