Development of a validated LC–MS/MS method for the determination of ailanthone in rat plasma with application to pharmacokinetic study

Chen, Ang; Qin, Xuan; Lu, Jian; Yi, Zhengfang; Liu, Mingyao; Wang, Xin

doi:10.1016/j.jpba.2014.10.022

Cited by 10 publications

(7 citation statements)

References 19 publications

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“…Ailanthone is a kind of quassinoids, which is extracted from the wide‐known Chinese medicine ailanthus 6. Ailanthone has a wide range of biological activities, including anti‐inflammatory, antimalaria, antiallergic, antiulcer, and antimicrobial, as well as antiproliferative effects on various cancer cells 7–9. In addition, many studies have shown that ailanthone has inhibitory effects on many cancer cell lines in vitro, including HepG2, Hep3B, r‐hepg2, HeLa, Huh‐7, SGC‐7901, and MCF‐7 6,10,11.…”

Section: Introductionmentioning

confidence: 99%

Retracted: Ailanthone exerts an antitumor function on the development of human lung cancer by upregulating microRNA‐195

2018

J of Cellular Biochemistry

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Background: Lung cancer is a common leading cause of cancer-related death worldwide. Ailanthone, a natural compound isolated from Chinese herb Ailanthus altissima, has been reported to exert antiproliferative effects on various cancer cells. Methods: The present study aimed to investigate the role of ailanthone in the lung cancer cells and the correlation between the ailanthone and microRNA (miR)-195. The cell viability, proliferation, and apoptosis were determined by cell counting kit-8 assay, bromodeoxyuridine incorporation method, annexin Vfluorescein isothiocyanate/propidium iodide assay, respectively. Apoptosis-and autophagy-related proteins, as well as regulatory factors in the signaling pathways, were analyzed by Western blot method. The expression of miR-195 was quantified by quantitative reverse transcription-polymerase chain reaction. Results:The results confirmed that ailanthone was involved in the lung cancer cell progress by inhibiting cell viability and proliferation, but promoted cell apoptosis and autophagy. We also found that ailanthone upregulated the expression of miR-195.Further, the downregulated miR-195 inhibited the apoptosis and autophagy induced by ailanthone. Moreover, our studies revealed that miR-195 inhibitor promoted the phosphorylation of PI3K, AKT, JAK, and STAT3, which was inhibited by ailanthone.Conclusion: All these findings suggest that ailanthone plays key roles in lung cancer progress and is closely correlated with miR-195 expression.

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Section: Introductionmentioning

confidence: 99%

Retracted: Ailanthone exerts an antitumor function on the development of human lung cancer by upregulating microRNA‐195

2018

J of Cellular Biochemistry

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“…Our previous studies have shown that the pharmacokinetic profiles of AIL in rats after intravenous (i.v.) administration exhibit linear pharmacokinetics37. Here we found that AIL was absorbed quickly, eliminated rapidly and distributed widely in tissues after oral administration (Fig.…”

Section: Resultsmentioning

confidence: 56%

“…Pharmacokinetic studies in vivo 37 and CYP-associated metabolic studies in vitro 56 were performed using the method reported previously in our laboratory. In this study, the effects of AIL on CYP activities were investigated using rat and human liver microsomes, employing phenacetin (CYP1A2), tolbutamide (CYP2C9/11), dextromethorphan (CYP2D1/6), chlorzoxazone (CYP2E1) and testosterone (CYP3A2/4) as the probe substrates.…”

Section: Methodsmentioning

confidence: 99%

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Ailanthone targets p23 to overcome MDV3100 resistance in castration-resistant prostate cancer

Peng

Wang

et al. 2016

Nat Commun

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Androgen receptor (AR) antagonist MDV3100 is the first therapeutic approach in treating castration-resistant prostate cancer (CRPC), but tumours frequently become drug resistant via multiple mechanisms including AR amplification and mutation. Here we identify the small molecule Ailanthone (AIL) as a potent inhibitor of both full-length AR (AR-FL) and constitutively active truncated AR splice variants (AR-Vs). AIL binds to the co-chaperone protein p23 and prevents AR's interaction with HSP90, thus resulting in the disruption of the AR-chaperone complex followed by ubiquitin/proteasome-mediated degradation of AR as well as other p23 clients including AKT and Cdk4, and downregulates AR and its target genes in PCa cell lines and orthotopic animal tumours. In addition, AIL blocks tumour growth and metastasis of CRPC. Finally, AIL possesses favourable drug-like properties such as good bioavailability, high solubility, lack of CYP inhibition and low hepatotoxicity. In general, AIL is a potential candidate for the treatment of CRPC.

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“…Interestingly, the antitumor effect was fully maintained when the drug was given orally at 5 mg/kg. The drug displays favorable pharmacokinetic properties (A. Chen et al, 2015), being quickly absorbed, eliminated, and distributed to organs after oral injection; the oral bioavailability is good (25%). The activity was attributed to the capacity of AIT to induce the downregulation and degradation of the androgen receptor (AR).…”

Section: In Vivo Antitumor Activity Of Aitmentioning

confidence: 99%

Anticancer properties and mechanism of action of the quassinoid ailanthone

Bailly

2020

Phytotherapy Research

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Ailanthone (AIT) is a quassinoid natural product isolated from the worldwide‐distributed plant Ailanthus altissima. The drug displays multiple pharmacological properties, in particular significant antitumor effects against a variety of cancer cell lines in vitro. Potent in vivo activities have been evidenced in mice bearing hepatocellular carcinoma, nonsmall cell lung cancer and castration‐resistant prostate cancer. This review focusses on the mechanism of action of AIT, notably to highlight the capacity of the drug to activate DNA damage responses, to inhibit the Hsp90 co‐chaperone p23 and to modulate the expression of several microRNA. The interconnexion between these effects is discussed. The unique capacity of AIT to downregulate oncogenic miR‐21 and to upregulate the tumor suppressor miRNAs miR‐126, miR‐148a, miR‐195, and miR‐449a is presented. AIT exploits several microRNAs to exert its anticancer effects in distinct tumor types. AIT is one of the rare antitumor natural products that binds to and strongly inhibits cochaperone p23, opening interesting perspectives to treat cancers. However, the toxicity profile of the molecule may limit its development as an anticancer drug, unless it can be properly formulated to prevent AIT‐induced gastro‐intestinal damages in particular. The antitumor properties of AIT and analogs are underlined, with the aim to encourage further pharmacological studies with this underexplored natural product and related quassinoids. Highlights Ailanthone (AIT) is an anticancer quassinoid isolated from Ailanthus altissima It inhibits proliferation and induces cell death of many cancer cell types The drug activates DNA damage response and targets p23 cochaperone Up or downregulation of several microRNA by AIT contributes to the anticancer activity Analogs or specific formulations must be developed to prevent the toxicity of AIT

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Development of a validated LC–MS/MS method for the determination of ailanthone in rat plasma with application to pharmacokinetic study

Cited by 10 publications

References 19 publications

Retracted: Ailanthone exerts an antitumor function on the development of human lung cancer by upregulating microRNA‐195

Retracted: Ailanthone exerts an antitumor function on the development of human lung cancer by upregulating microRNA‐195

Ailanthone targets p23 to overcome MDV3100 resistance in castration-resistant prostate cancer

Anticancer properties and mechanism of action of the quassinoid ailanthone

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