P2X7 receptor involved in antitumor activity of atractylenolide I in human cervical cancer cells

Han, Yanyan; Bai, Can; He, X; Ren, Qingling

doi:10.1007/s11302-022-09854-6

Cited by 7 publications

(6 citation statements)

References 43 publications

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“…This might also incline us to test higher doses (over 4 mg/kg) of ATL I in future studies. Accumulating evidence has indicated that ATL I has a promising effect on cancer treatment, at least including colon cancer, cervical cancer, and breast cancer [53][54][55][56][57]. Thus, this also inclines us to explore the effect of ATL 1 on treating the later stages of metabolic-associated fatty liver disease, such as liver fibrosis, and even liver cancer.…”

Section: Discussionmentioning

confidence: 99%

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ATL I, Acts as a SIRT6 Activator to Alleviate Hepatic Steatosis in Mice via Suppression of NLRP3 Inflammasome Formation

et al. 2022

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Accumulating evidence has highlighted that sirtuin-6 (SIRT6) plays an important role in hepatic gluconeogenesis and lipogenesis. We aim to investigate the underlying mechanisms and pharmacological interventions of SIRT6 on hepatic steatosis treatment. Herein, our results showed that atractylenolide I (ATL I) activated the deacetylase activity of SIRT6 to promote peroxisome proliferator-activated receptor alpha (PPARα) transcription and translation, while suppressing nuclear factor NF-kappa-B (NFκB)-induced NACHT, LRR, and PYD domains containing protein 3 (NLRP3) inflammasome formation. Together, these decreased the infiltration of F4/80 and CD11B positive macrophages, accompanied by decreased mRNA expression and serum levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL6), and interleukin-1 beta (IL1β). Additionally, these changes decreased sterol regulatory element-binding protein-1c (SREBP-1c) expression, while restoring carnitine O-palmitoyltransferase 1a (Cpt1a) expression, to decrease the size of adipocytes and adipose deposition, which, in turn, reversed high-fat diet (HFD)-induced liver weight and body weight accumulation in C57 mice. SIRT6 knockout or hepatic SIRT6 knockout in C57 mice largely abolished the effect of ATL I on ameliorating hepatic steatosis. Taken together, our results suggest that ATL I acts as a promising compound that activates SIRT6/PPARα signaling and attenuates the NLRP3 inflammasome to ameliorate hepatic inflammation and steatosis.

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Section: Discussionmentioning

confidence: 99%

“…The MPHs were extracted by an in situ two-step perfusion method, as previously reported [54]. In brief, mice were anesthetized with 10% chloral hydrate, and the limbs were fixed.…”

Section: Isolation Of Mouse Primary Hepatocytes (Mphs)mentioning

confidence: 99%

ATL I, Acts as a SIRT6 Activator to Alleviate Hepatic Steatosis in Mice via Suppression of NLRP3 Inflammasome Formation

et al. 2022

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“…Moreover, other studies showed a decreased level of the full-length variant of the P2X7 receptor, where the level of reduction correlated with the degree of tumor development (Li et al, 2007). Similarly, in the two separate human cervical cancer cell lines, the P2X7 receptor would become engaged in the anticancer activity of atractylenolide-I (Han et al, 2022). There are also reports indicating the coexistence of different P2X7 receptor isoforms in cervical cancer cells, where an alternative P2XJ receptor splicing variant may form non-functional trimers with the P2X7A variant (Feng et al, 2006).…”

Section: P2x7 In Cervical Cancermentioning

confidence: 95%

P2X7 receptor in normal and cancer cells in the perspective of nucleotide signaling

2022

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Nucleotides are the most common compounds produced constantly by living organisms. They are involved in most cellular processes like the synthesis of other nucleotides and nucleic acids, generation of energy needed for the maintenance of cells, and molecular signaling. In the 70s sir. Geoffrey Burstock discovered a new class of transmembrane proteins – nucleotide receptors responding to nucleotides and their derivatives. For historical reasons, we distinguish two main classes of nucleotide receptors: P1 – which are G protein-coupled adenosine receptors, and P2 – nucleotide receptors that respond to ATP and its derivatives. Additionally, the P2 receptors family can be divided into two subgroups: P2Y – G protein-coupled receptors and P2X cation channel receptors. This paper focuses mainly on the most researched receptor in the nucleotide receptors family – the P2X7 receptor – presenting it in the background of the nucleotide signaling landscape. Almost thirty years of extensive studies on the receptor contributed to understanding protein structure, splicing variants, and mechanism of action in somatic cells. Despite such a wide spectrum of research, the role of the receptor in cancer progression is still undetermined. In many reports, we can find information about the anti-tumorigenic role of this receptor caused by activation of the cell death mechanism after membrane pore formation. These results, however, contradict other studies in which the same receptor is known to promote cancer development through stimulation of proliferation and activation of pro-survival pathways. Ultimately, all this gathered knowledge points to two faces of the receptor in tumor progression. Therefore, we do provide a comprehensive overview of the topic. Finally, we also try to systemize previous and recent literature about the role of this receptor in somatic and cancer cells and provide access to it in the form of a convenient table.

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“…By inhibiting the expression of Hsp27, ATL I can inhibit the proliferation of prostate carcinoma cells and enhance the efficacy of cabotinib [ 59 ]. Han et al [ 60 ] determined that ATL I decreased the proliferation of human cervical cancer cells Hela and SiHa, and that combination treatment with the P2X7R receptor antagonist JNJ increased cytostatic effect on SiHa cells.…”

Section: Pharmacological Effects Of Atractylenolidesmentioning

confidence: 99%

Chemical Constitution, Pharmacological Effects and the Underlying Mechanism of Atractylenolides: A Review

Xie

Lin

et al. 2023

Molecules

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Atractylenolides, comprising atractylenolide I, II, and III, represent the principal bioactive constituents of Atractylodes macrocephala, a traditional Chinese medicine. These compounds exhibit a diverse array of pharmacological properties, including anti-inflammatory, anti-cancer, and organ-protective effects, underscoring their potential for future research and development. Recent investigations have demonstrated that the anti-cancer activity of the three atractylenolides can be attributed to their influence on the JAK2/STAT3 signaling pathway. Additionally, the TLR4/NF-κB, PI3K/Akt, and MAPK signaling pathways primarily mediate the anti-inflammatory effects of these compounds. Atractylenolides can protect multiple organs by modulating oxidative stress, attenuating the inflammatory response, activating anti-apoptotic signaling pathways, and inhibiting cell apoptosis. These protective effects extend to the heart, liver, lung, kidney, stomach, intestine, and nervous system. Consequently, atractylenolides may emerge as clinically relevant multi-organ protective agents in the future. Notably, the pharmacological activities of the three atractylenolides differ. Atractylenolide I and III demonstrate potent anti-inflammatory and organ-protective properties, whereas the effects of atractylenolide II are infrequently reported. This review systematically examines the literature on atractylenolides published in recent years, with a primary emphasis on their pharmacological properties, in order to inform future development and application efforts.

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P2X7 receptor involved in antitumor activity of atractylenolide I in human cervical cancer cells

Cited by 7 publications

References 43 publications

ATL I, Acts as a SIRT6 Activator to Alleviate Hepatic Steatosis in Mice via Suppression of NLRP3 Inflammasome Formation

ATL I, Acts as a SIRT6 Activator to Alleviate Hepatic Steatosis in Mice via Suppression of NLRP3 Inflammasome Formation

P2X7 receptor in normal and cancer cells in the perspective of nucleotide signaling

Chemical Constitution, Pharmacological Effects and the Underlying Mechanism of Atractylenolides: A Review

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