Umbelliferone Decreases Intracellular pH and Sensitizes Melanoma Cell Line A375 to Dacarbazin. Comparison with Acetazolamide

Puech, Clémentine; Chatard, Morgane; Felder‐Flesch, Delphine; Prévôt, Nathalie; Perek, Nathalie

doi:10.2174/1874467208666161128152518

Cited by 10 publications

(6 citation statements)

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“…Furthermore, this isoform serves as a driving force in cytosolic pH regulation . It has been reported that the resting intracellular pH of cells is affected by CA inhibitors, and this change varies depending on the cell type. − …”

Section: Resultsmentioning

confidence: 99%

In Situ Photoregulation of Carbonic Anhydrase Activity Using Azobenzenesulfonamides

et al. 2018

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We report two small molecule azobenzenesulfonamide probes, CAP1 and CAP2, capable of photomodulating the activity of carbonic anhydrase (CA) on demand. In the trans form, CAP azobenzene probes adopt a linear shape, making them suitable for occupying the CA active site and interacting with Zn 2+ , thereby inhibiting enzyme activity. Following irradiation with either 365 or 410 nm light, the CAP probes isomerize to their cis form. Because of the change in steric profile, the probe exits the active site, and the activity of the enzyme is restored. The cis isomer can revert back to the trans isomer through thermal relaxation or via photoirradiation with 460 nm light and thereby inhibit protein activity again. This process can be repeated multiple times without any photodegradation and thus can be used to inhibit or activate the protein reversibly. Importantly, we demonstrate our ability to apply CAP azobenzene probes to regulate CA activity both in an isolated protein solution and in live cells, where the two isomers of CAP1 differentially regulate the intracellular cytosolic pH.

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Section: Resultsmentioning

confidence: 99%

In Situ Photoregulation of Carbonic Anhydrase Activity Using Azobenzenesulfonamides

et al. 2018

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“…Human carbonic anhydrases (EC 4.2.1.1) types IX and XII are overexpressed in a variety of cancer types and play a large role in pH regulation required to drive metastasis and growth, with greater importance to solid hypoxic tumors (54). Drugs such as CAIX inhibitor FC16-670A or any other compound that can down-regulate carbonic anhydrases will inevitably reduce the capacity of tumor cells to maintain acid-base equilibrium and thereby deal a vital blow to cancer survival, growth and resistance (e.g., sulfamides (acetazolamide) and coumarins (umbelliferon)) (55,56). Combined efficacy of chemotherapy drug treatment is greater when combined with an inhibitor of carbonic acids, proton pumps (57), or HDACs (58), all of which could reduce tumor acidity.…”

Section: Discussionmentioning

confidence: 99%

Whole-transcriptomic Profile of SK-MEL-3 Melanoma Cells Treated with the Histone Deacetylase Inhibitor: Trichostatin A

Mazzio

Soliman

2018

Cancer Genomics Proteomics

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“…Many cancer cell lines express a number of CAs, including transmembrane hCAIX, hCAXII, and cytosolic hCAII under hypoxic conditions and these CAs play vital roles in manipulating the pH i of cancer cells, thus promoting the growth and metathesis of tumors. According to previous studies, inhibition of CAs can lead to cellular pH i manipulation, which is a cell-type dependent effect. − …”

Section: Resultsmentioning

confidence: 98%

A Versatile Strategy to Manipulate and Probe Native Carbonic Anhydrases In Cellulo Utilizing Two-Step Ligand-Directed Functionalization

Wang

2023

ACS Chem. Biol.

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Elucidating the biological logistics and functional interplay of proteins in their natural context has long been a great challenge in biological research. Chemical modification of proteins allows understanding of their roles and their interactions. Over decades, numerous strategies have been developed to modify target proteins with desired probes in test tubes and even biological systems. Nevertheless, these approaches require the design and synthesis of different probes for different applications, even for the same target protein, which is very time- and labor-consuming. Herein, we developed a general two-step protein functionalization strategy that utilizes ligand-directed chemistry to modify a clickable tag on the intact protein in the first step. Then, the desired functional moiety can be conjugated onto the target protein via a simple bioorthogonal click reaction in the second step, thus achieving probing and activity regulation of the target protein. In this work, carbonic anhydrase (CA) was chosen as our model protein for functionalization. We successfully labeled endogenous CAs with fluorophores to allow cellular imaging. In addition, a photoswitchable ligand was conjugated to CAs such that its activity could be manipulated in a light-responsive manner.

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Umbelliferone Decreases Intracellular pH and Sensitizes Melanoma Cell Line A375 to Dacarbazin. Comparison with Acetazolamide

Cited by 10 publications

References 0 publications

In Situ Photoregulation of Carbonic Anhydrase Activity Using Azobenzenesulfonamides

In Situ Photoregulation of Carbonic Anhydrase Activity Using Azobenzenesulfonamides

Whole-transcriptomic Profile of SK-MEL-3 Melanoma Cells Treated with the Histone Deacetylase Inhibitor: Trichostatin A

A Versatile Strategy to Manipulate and Probe Native Carbonic Anhydrases In Cellulo Utilizing Two-Step Ligand-Directed Functionalization

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