A synthetic decursin analog with increased in vivo stability suppresses androgen receptor signaling in vitro and in vivo

Zhang, Yong; Shaik, Ahmad Ali; Xing, Chengguo; Chai, Yubo; Li, Li; Zhang, Jinhui; Zhang, Wei; Kim, Sung Hoon; Lü, Junxuan; Jiang, Cheng

doi:10.1007/s10637-011-9738-x

Cited by 17 publications

(10 citation statements)

References 29 publications

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“…Galbanic acid was isolated from the gum resin of F. assafoetida purchased from Hanil Herbal Shop (Seoul, Korea). 1,2,3,4,6-penta-O-galloyl-beta-d-glucose (PGG) was isolated from the gallnut of Rhus chinensis MILL as described previously 25, 26.…”

Section: Methodsmentioning

confidence: 99%

Blockage of epithelial to mesenchymal transition and upregulation of let 7b are critically involved in ursolic acid induced apoptosis in malignant mesothelioma cell

Sohn¹,

Won²,

Lee³

et al. 2016

Int. J. Biol. Sci.

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Malignant pleural mesothelioma (MPN), which is caused by asbestos exposure, is one of aggressive lung tumors. In the present study, we elucidated the anti-tumor mechanism of ursolic acid in malignant mesotheliomas. Ursolic acid significantly exerted cytotoxicity in a time and dose dependent manner in H28, H2452 and MSTO-211H mesothelioma cells and inhibited cell proliferation by colony formation assay in a dose-dependent fashion. Also, ursolic acid treatment accumulated the sub-G1 population, attenuated the expression of procapase 9, cyclin D1, pAKT, p-glycogen synthase kinase 3-alpha/beta (pGSK3α/β), β-catenin and nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) and also cleaved caspase 3 and poly (ADP-ribose) polymerase (PARP) in mesothelioma cells. Furthermore, ursolic acid treatment blocked epithelial and mesenchymal transition (EMT) molecules by activating E-cadherin as an epithelial marker and attenuating Vimentin, and Twist as mesenchymal molecules. Interestingly, miRNA array revealed that 23 miRNAs (>2 folds) including let-7b and miRNA3613-5p, miRNA134 and miRNA196b were significantly upregulated while 33 miRNAs were downregulated in ursolic acid treated H2452 cells. Furthermore, overexpression of let 7b using let-7b mimics enhanced the antitumor effect of ursolic acid to attenuate the expression of procaspases 3, pro-PARP, pAKT, β-catenin and Twist and increase sub-G1 accumulation in H2452 mesothelioma cells. Overall, our findings suggest that ursolic acid induces apoptosis via inhibition of EMT and activation of let7b in mesothelioma cells as a potent chemotherapeutic agent for treatment of malignant mesotheliomas.

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Section: Methodsmentioning

confidence: 99%

Blockage of epithelial to mesenchymal transition and upregulation of let 7b are critically involved in ursolic acid induced apoptosis in malignant mesothelioma cell

Sohn¹,

Won²,

Lee³

et al. 2016

Int. J. Biol. Sci.

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“…Many studies reveal that Curcumin, [48] (−)-epigallocatechin-3-gallate, a major constituent of green tea [49], decursin [50], capsaicin [51] and the potent PSA inhibitor boron [52] fall in this category.…”

Section: Psa Lowering Substancesmentioning

confidence: 99%

Role of Prostate Specific Antigen (PSA) in Pathogenesis of Prostate Cancer

Altuwaijri¹

2012

JCT

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Prostate cancer (PCa) is most common diagnosed cancer in men and it is second most common cause of male cancer death. Many factors have been implicated in the pathogenesis of PCa. Although many papers have discussed the prostate specific antigen (PSA) as biomarker of PCa, very few have addressed its rule in the carcinogenesis, metastasis and invasion of PCa. In this article we will review the pathological role of PSA, as a potential target in the therapeutics of PCa.

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“…Decursin and DA (decursin/DA) were purified together from ethanol extracts of the root of Angelica gigas Nakai by silica column chromatography as described [11] with modifications [23]. Decursinol was prepared by hydrolysis of decursin/DA [23]. The purity of the above compounds was verified by HPLC which was shown to be higher than 95% (data not shown).…”

Section: Reagents and Chemicalsmentioning

confidence: 99%

Quantitative Determination of Decursin, Decursinol Angelate, and Decursinol in Mouse Plasma and Tumor Tissue Using Liquid-Liquid Extraction and HPLC

Li¹,

Zhang²,

Shaik³

et al. 2011

Planta Med

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The pyranocoumarin compound decursin and its isomer decursinol angelate (DA) are the major hydrophobic phytochemicals in the root of Angelica gigas Nakai (AGN, Korean Angelica), a major traditional medicinal herb. The ethanol extract of AGN and especially the purified decursin and DA have been shown to exhibit antitumor activities by our collaborative team and others. Although decursinol has been identified as a major hydrolysis metabolite of decursin and DA in vivo in previous pharmacokinetic studies with mouse and rat, other recently published results sharply disputed this conclusion. In this study, we set up a practical method for the concurrent analysis of decursin, DA, and decursinol in mouse plasma and tumor tissues by liquid-liquid extraction and HPLC-UV and applied the method to several animal experiments. Plasma or tumor homogenate was extracted directly with ethyl acetate. The extraction efficiency for decursin/DA (quantitated together) and decursinol was between 82-95 % in both mouse plasma and tumor homogenate. The lower limit of quantitation (LLOQ) was approximately 0.25 µg/mL for decursin/DA and 0.2 µg/mL for decursinol in mouse plasma. In a pilot pharmacokinetic study, male C57BL/6 mice were given a single dose of 4.8 mg decursin/DA mixture (~240 mg/kg) per mouse either by oral gavage or intraperitoneal injection. Maximum plasma concentrations for decursin/DA and decursinol were 11.2 and 79.7 µg/mL, respectively, when decursin/DA was administered via intraperitoneal injection, and 0.54 and 14.9 µg/mL via oral gavage. Decursin/DA and decursinol contents in the tumor tissues from nude mouse xenografts correlated very well with those in plasma. Overall, our results confirm the conclusion that the majority of decursin/DA hydrolyze to decursinol in rodent models with a tiny fraction remaining as the intact compounds administered.

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A synthetic decursin analog with increased in vivo stability suppresses androgen receptor signaling in vitro and in vivo

Cited by 17 publications

References 29 publications

Blockage of epithelial to mesenchymal transition and upregulation of let 7b are critically involved in ursolic acid induced apoptosis in malignant mesothelioma cell

Blockage of epithelial to mesenchymal transition and upregulation of let 7b are critically involved in ursolic acid induced apoptosis in malignant mesothelioma cell

Role of Prostate Specific Antigen (PSA) in Pathogenesis of Prostate Cancer

Quantitative Determination of Decursin, Decursinol Angelate, and Decursinol in Mouse Plasma and Tumor Tissue Using Liquid-Liquid Extraction and HPLC

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