Carbonic anhydrase IX: A tumor acidification switch in heterogeneity and chemokine regulation

Queen, Aarfa; Bhutto, Humaira Naaz; Yousuf, Mohd; Syed, Mansoor Ali; Hassan, Md. Imtaiyaz

doi:10.1016/j.semcancer.2022.01.001

Cited by 43 publications

(19 citation statements)

References 209 publications

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“…Carbonic anhydrases (CAs) catalyze a reversible reaction in which CO 2 and water are transformed into intracellular bicarbonate and a proton is released extracellularly [301]. Tumor cells with a high glycolysis rate produce plentiful lactate which exists in the form of lactate-(Lac-) and H + .…”

Section: Carbonic Anhydrasementioning

confidence: 99%

Warburg effect in colorectal cancer: the emerging roles in tumor microenvironment and therapeutic implications

et al. 2022

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Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death worldwide. Countless CRC patients undergo disease progression. As a hallmark of cancer, Warburg effect promotes cancer metastasis and remodels the tumor microenvironment, including promoting angiogenesis, immune suppression, cancer-associated fibroblasts formation and drug resistance. Targeting Warburg metabolism would be a promising method for the treatment of CRC. In this review, we summarize information about the roles of Warburg effect in tumor microenvironment to elucidate the mechanisms governing Warburg effect in CRC and to identify novel targets for therapy.

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Section: Carbonic Anhydrasementioning

confidence: 99%

Warburg effect in colorectal cancer: the emerging roles in tumor microenvironment and therapeutic implications

et al. 2022

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“…Tumor cells have greatly elevated levels of the H + -ATPases, Na + -H + exchanger NHE1, and monocarboxylate-H + efux cotransporters MCT1 and MCT4, and these factors all contribute to H+ efux [86]. Additionally, the preservation of low pH in TME is also aided by carbonic anhydrase 9 (CA9), which is overexpressed in several cancer types [87].…”

Section: Targeting the Acidic Tmementioning

confidence: 99%

Targeting Tumor Microenvironment by Metal Peroxide Nanoparticles in Cancer Therapy

Mbugua

2022

Bioinorganic Chemistry and Applications

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Solid tumors have a unique tumor microenvironment (TME), which includes hypoxia, low acidity, and high hydrogen peroxide and glutathione (GSH) levels, among others. These unique factors, which offer favourable microenvironments and nourishment for tumor development and spread, also serve as a gateway for specific and successful cancer therapies. A good example is metal peroxide structures which have been synthesized and utilized to enhance oxygen supply and they have shown great promise in the alleviation of hypoxia. In a hypoxic environment, certain oxygen-dependent treatments such as photodynamic therapy and radiotherapy fail to respond and therefore modulating the hypoxic tumor microenvironment has been found to enhance the antitumor impact of certain drugs. Under acidic environments, the hydrogen peroxide produced by the reaction of metal peroxides with water not only induces oxidative stress but also produces additional oxygen. This is achieved since hydrogen peroxide acts as a reactive substrate for molecules such as catalyse enzymes, alleviating tumor hypoxia observed in the tumor microenvironment. Metal ions released in the process can also offer distinct bioactivity in their own right. Metal peroxides used in anticancer therapy are a rapidly evolving field, and there is good evidence that they are a good option for regulating the tumor microenvironment in cancer therapy. In this regard, the synthesis and mechanisms behind the successful application of metal peroxides to specifically target the tumor microenvironment are highlighted in this review. Various characteristics of TME such as angiogenesis, inflammation, hypoxia, acidity levels, and metal ion homeostasis are addressed in this regard, together with certain forms of synergistic combination treatments.

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“… 9 , 10 Moreover, CA-IX is a hypoxia-associated isoform that plays a crucial role in extracellular acidification of the solid tumour, contributing to tumour progression. 11 , 12 On the other hand, CA-XII is overexpressed in a range of human tumours including gastric, ovarian, lung, and brain, whereas its expression in normal tissues is also restricted. 13–15 In addition, CA-XII expression is induced by oestrogen; hence this isoform is highly expressed in oestrogen receptor-positive breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Selenium-analogs based on natural sources as cancer-associated carbonic anhydrase isoforms IX and XII inhibitors

Astrain-Redín

Paoletti

Plano

et al. 2023

Journal of Enzyme Inhibition and Medicinal Chemistry

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In the relentless search for new cancer treatments, organoselenium compounds, and carbonic anhydrase (CA) inhibitors have emerged as promising drug candidates. CA isoforms IX and XII are overexpressed in many types of cancer, and their inhibition is associated with potent antitumor/antimetastatic effects. Selenium-containing compounds, particularly selenols, have been shown to inhibit tumour-associated CA isoforms in the nanomolar range since the properties of the selenium atom favour binding to the active site of the enzyme. In this work, two series of selenoesters (1a–19a and 1b–19b), which gathered NSAIDs, carbo/heterocycles, and fragments from natural products, were evaluated against hCA I, II, IX, and XII. Indomethacin (17b) and flufenamic acid (19b) analogs exhibited selectivity for tumour-associated isoform IX in the low micromolar range. In summary, selenoesters that combine NSAIDs with fragments derived from natural sources have been developed as promising nonclassical inhibitors of the tumour-associated CA isoforms.

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Carbonic anhydrase IX: A tumor acidification switch in heterogeneity and chemokine regulation

Cited by 43 publications

References 209 publications

Warburg effect in colorectal cancer: the emerging roles in tumor microenvironment and therapeutic implications

Warburg effect in colorectal cancer: the emerging roles in tumor microenvironment and therapeutic implications

Targeting Tumor Microenvironment by Metal Peroxide Nanoparticles in Cancer Therapy

Selenium-analogs based on natural sources as cancer-associated carbonic anhydrase isoforms IX and XII inhibitors

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