Targeting Sterol <i>O</i>-Acyltransferase/Acyl-CoA:Cholesterol Acyltransferase (ACAT): A Perspective on Small-Molecule Inhibitors and Their Therapeutic Potential

Bhattacharjee, Pinaki; Rutland, Nicholas; Iyer, Malliga R.

doi:10.1021/acs.jmedchem.2c01265

Cited by 9 publications

(8 citation statements)

References 212 publications

(465 reference statements)

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“…The anti-tumor effect of ACAT1 inhibitors should be further verified in more cancer types in vitro and vivo models to explore the cancer types that can be effectively treated with ACAT1 inhibitors. Clinical trials should be accelerated to evaluate the anti-tumor effects of more ACAT1 inhibitors in different cancer types ( 62 ).…”

Section: Implications For Targeting Acat1 In Anti-tumor Therapymentioning

confidence: 99%

Targeting ACAT1 in cancer: from threat to treatment

Sun,

Xiao

2024

Front. Oncol.

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Altered cholesterol metabolism has been identified as a critical feature of cancers. Cholesterol functions as the main component of cell membrane, cholesterol and is required for sustaining membrane integrity and mediating signaling transduction for cell survival. The intracellular level of cholesterol is dynamically regulated. Excessive cholesterol could be converted to less toxic cholesteryl esters by acyl-coenzyme A:cholesterol acyltransferases (ACATs). While ACAT2 has limited value in cancers, ACAT1 has been found to be widely participated in tumor initiation and progression. Moreover, due to the important role of cholesterol metabolism in immune function, ACAT1 is also essential for regulating anti-tumor immunity. ACAT1 inhibition may be exploited as a potential strategy to enhance the anti-tumor immunity and eliminate tumors. Herein, a comprehensive understanding of the role of ACAT1 in tumor development and anti-tumor immunity may provide new insights for anti-tumor strategies.

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Section: Implications For Targeting Acat1 In Anti-tumor Therapymentioning

confidence: 99%

Targeting ACAT1 in cancer: from threat to treatment

Sun,

Xiao

2024

Front. Oncol.

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“…LDL is isolated from LDLR in endosome and further transferred to lysosome [ 6 ]. Free cholesterol was released from lysosome and formed cholesterol ester mediated by sterol O-acyltransferase (SOAT) [ 7 ]. Moreover, Niemann–Pick C1-like 1 (NPC1L1) facilitates uptake of dietary cholesterol by small intestinal cells [ 8 ].…”

Section: Overview Of Cholesterol Metabolismmentioning

confidence: 99%

Dysregulated cholesterol regulatory genes in hepatocellular carcinoma

Cao,

Liu

2023

Eur J Med Res

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Cholesterol is an indispensable component in mammalian cells, and cholesterol metabolism performs important roles in various biological activities. In addition to the Warburg effect, dysregulated cholesterol metabolism is one of the metabolic hallmarks of several cancers. It has reported that reprogrammed cholesterol metabolism facilitates carcinogenesis, metastasis, and drug-resistant in various tumors, including hepatocellular carcinoma (HCC). Some literatures have reported that increased cholesterol level leads to lipotoxicity, inflammation, and fibrosis, ultimately promoting the development and progression of HCC. Contrarily, other clinical investigations have demonstrated a link between higher cholesterol level and lower risk of HCC. These incongruent findings suggest that the connection between cholesterol and HCC is much complicated. In this report, we summarize the roles of key cholesterol regulatory genes including cholesterol biosynthesis, uptake, efflux, trafficking and esterification in HCC. In addition, we discuss promising related therapeutic targets for HCC.

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“…In addition, Wang et al determined that berberine (BBR), a principal bioactive compound in Coptis chinensis and many other medicinal plants, decreases cholesterol levels in rats through multiple mechanisms, including the inhibition of cholesterol absorption 72 . In the process of exploring this mechanism, the role of acetyl-CoA cholesterol acyltransferase (ACAT) (an enzyme that catalyzes cholesterol esterification in the cell and accelerates intestinal absorption) in mediating the regulation of cholesterol absorption by TCM has attracted the attention of researchers 73 . Hawthorn (Crataegus pinnatifida) is an edible fruit used in Chinese medicine to lower blood lipid levels.…”

Section: Mechanism Of Tcm In Regulating Lipid Metabolismmentioning

confidence: 99%

Lipid metabolic reprogramming by traditional Chinese medicine and its role in effective cancer therapy

Liu¹,

Li²,

Dong³

et al. 2023

J. Cancer

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Epidemiological data have shown a positive correlation between lipid levels and tumor occurrence, such as the correlation between tumor frequency and aggressiveness, and cardiovascular disease, obesity, type 2 diabetes mellitus, and hyperinsulinemia. Therefore, reducing fat accumulation or weakening lipid metabolism may affect the carcinogenic processes of cells. Many studies have shown that traditional Chinese Medicine (TCM) has obvious advantages over traditional therapies in terms of fewer side effects, lower toxicity, and lower economic burden. This paper reviews the mechanism by which TCM regulates lipid metabolism and its antitumor effect through this regulation, with the aim of elucidating the bioactive compounds in TCM with good efficacy and few side effects that can provide promising therapeutic drugs for targeting lipid metabolism reprogramming in cancer.

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Targeting Sterol O-Acyltransferase/Acyl-CoA:Cholesterol Acyltransferase (ACAT): A Perspective on Small-Molecule Inhibitors and Their Therapeutic Potential

Cited by 9 publications

References 212 publications

Targeting ACAT1 in cancer: from threat to treatment

Targeting ACAT1 in cancer: from threat to treatment

Dysregulated cholesterol regulatory genes in hepatocellular carcinoma

Lipid metabolic reprogramming by traditional Chinese medicine and its role in effective cancer therapy

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