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Dr. Bianca Maria Rotoli

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Laboratory of General Pathology, Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy
Interests: molecular pathogenetic mechanisms in inherited disorders; bronchial epithelium; immune cells; amino acid transport through plasma membrane; solute transporters

Special Issue Information

Dear Colleague,

OCTs are solute link-carriers, belonging to the SLC22A family of transporters; they are often found in epithelial membranes and they mediate the uptake and secretion of organic cations. Based on the driving force for substrate transport, they can be classified into the electrogenic transporters OCT1 (SLC22A1), OCT2 (SLC22A2), OCT3 (SLC22A3), and the pH-dependent novel transporters OCTN1 (SLC22A4) and OCTN2 (SLC22A5). While OCTNs are mainly known for their ability to mediate carnitine influx, OCTs can translocate small (<500 Da) organic cations with broad, overlapping affinities for a wide range of substrates. The presence of these transporters is widely documented in the liver, kidneys, intestine, lung, and blood–brain barrier.

This Special Issue will create a comprehensive collection of the most recent advances concerning the expression and function of OCTs under physiological and pathological conditions. Topics of the Issue may include, but are not limited to the following:

The role of OCTs in the maintenance of cell/tissue homeostasis and function
The modulation of OCTs expression and function
Defects in OCTs and human diseases
Pharmacological relevance of OCTs and their interaction with known and candidate drugs.

Dr. Bianca Maria Rotoli
Guest Editor

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Keywords

organic cation transporters (OCTs)
membrane transport and regulation
tetraethylammonium (TEA)
methyl 4-phenylpiridinium (MPP+)
carnitine
human diseases
pharmacological relevance

Published Papers (2 papers)

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Research

13 pages, 1498 KiB

Open AccessArticle

In Vitro Inhibition of Renal OCT2 and MATE1 Secretion by Antiemetic Drugs

by Blessy George, Xia Wen, Edgar A. Jaimes, Melanie S. Joy and Lauren M. Aleksunes

Int. J. Mol. Sci. 2021, 22(12), 6439; https://doi.org/10.3390/ijms22126439 - 16 Jun 2021

Cited by 5 | Viewed by 2414

Abstract

The organic cation transporter 2 (OCT2) and multidrug and toxin extrusion protein 1 (MATE1) mediate the renal secretion of drugs. Recent studies suggest that ondansetron, a 5-HT₃ antagonist drug used to prevent nausea and vomiting, can inhibit OCT2- and MATE1-mediated transport. The purpose of this study was to test the ability of five 5-HT₃ antagonist drugs to inhibit the OCT2 and MATE1 transporters. The transport of the OCT2/MATE1 probe substrate ASP⁺ was assessed using two models: (1) HEK293 kidney cells overexpressing human OCT2 or MATE1, and (2) MDCK cells transfected with human OCT2 and MATE1. In HEK293 cells, the inhibition of ASP⁺ uptake by OCT2 listed in order of potency was palonosetron (IC₅₀: 2.6 μM) > ondansetron > granisetron > tropisetron > dolasetron (IC₅₀: 85.4 μM) and the inhibition of ASP⁺ uptake by MATE1 in order of potency was ondansetron (IC₅₀: 0.1 μM) > palonosetron = tropisetron > granisetron > dolasetron (IC₅₀: 27.4 μM). Ondansetron (0.5–20 μM) inhibited the basolateral-to-apical transcellular transport of ASP⁺ up to 64%. Higher concentrations (10 and 20 μM) of palonosetron, tropisetron, and dolasetron similarly reduced the transcellular transport of ASP⁺. In double-transfected OCT2-MATE1 MDCK cells, ondansetron at concentrations of 0.5 and 2.5 μM caused significant intracellular accumulation of ASP⁺. Taken together, these data suggest that 5-HT₃ antagonist drugs may inhibit the renal secretion of cationic drugs by interfering with OCT2 and/or MATE1 function. Full article

(This article belongs to the Special Issue Organic Cation Transporters (OCTs))

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31 pages, 8059 KiB

Open AccessArticle

Incorporation of Sulfonamide Moiety into Biguanide Scaffold Results in Apoptosis Induction and Cell Cycle Arrest in MCF-7 Breast Cancer Cells

by Magdalena Markowicz-Piasecka, Karol Sadowski, Johanna Huttunen, Joanna Sikora and Kristiina M. Huttunen

Int. J. Mol. Sci. 2021, 22(11), 5642; https://doi.org/10.3390/ijms22115642 - 26 May 2021

Cited by 3 | Viewed by 3062

Abstract

Metformin, apart from its glucose-lowering properties, has also been found to demonstrate anti-cancer properties. Anti-cancer efficacy of metformin depends on its uptake in cancer cells, which is mediated by plasma membrane monoamine transporters (PMAT) and organic cation transporters (OCTs). This study presents an analysis of transporter mediated cellular uptake of ten sulfonamide-based derivatives of metformin in two breast cancer cell lines (MCF-7 and MDA-MB-231). Effects of these compounds on cancer cell growth inhibition were also determined. All examined sulfonamide-based analogues of metformin were characterized by greater cellular uptake in both MCF-7 and MDA-MB-231 cells, and stronger cytotoxic properties than those of metformin. Effective intracellular transport of the examined compounds in MCF-7 cells was accompanied by high cytotoxic activity. For instance, compound 2 with meta-methyl group in the benzene ring inhibited MCF-7 growth at micromolar range (IC₅₀ = 87.7 ± 1.18 µmol/L). Further studies showed that cytotoxicity of sulfonamide-based derivatives of metformin partially results from their ability to induce apoptosis in MCF-7 and MDA-MB-231 cells and arrest cell cycle in the G0/G1 phase. In addition, these compounds were found to inhibit cellular migration in wound healing assay. Importantly, the tested biguanides are more effective in MCF-7 cells at relatively lower concentrations than in MDA-MB-231 cells, which proves that the effectiveness of transporter-mediated accumulation in MCF-7 cells is related to biological effects, including MCF-7 cell growth inhibition, apoptosis induction and cell cycle arrest. In summary, this study supports the hypothesis that effective transporter-mediated cellular uptake of a chemical molecule determines its cytotoxic properties. These results warrant a further investigation of biguanides as putative anti-cancer agents. Full article

(This article belongs to the Special Issue Organic Cation Transporters (OCTs))

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