Seven Quassinoids from Fructus Bruceae with Cytotoxic Effects on Pancreatic Adenocarcinoma Cell Lines

Zhao, Ming; Lau, Sing; Leung, Po Sing; T., C.; Lin, Zhi Xiu

doi:10.1002/ptr.3477

Cited by 41 publications

(36 citation statements)

References 20 publications

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“…Constituents within this herb are well documented and include bruceine D which is toxic to pancreatic cancer cell lines (Panc‐1, SW1990, Capan‐1/2 cells) some reporting comparable efficacy to that of camptothecin and gemcitabine (Liu et al ., ). The alcohol extract of the fruit contains diverse quassinoids including brusatol, bruceantin, and bruceine A, which are itself effective against growth and survival of pancreatic cancers, (Zhao et al ., ) induce apoptosis associated with elevation of tumor suppressor proteins (Gao et al ., ), and are believed to be promising against pancreatic cancer (Pan et al ., ) (Lau et al ., ).…”

Section: Discussionmentioning

confidence: 99%

High Throughput Screening of Natural Products for Anti‐mitotic Effects in MDA‐MB‐231 Human Breast Carcinoma Cells

Mazzio

Badisa

Mack

et al. 2013

Phytotherapy Research

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Some of the most effective anti-mitotic microtubule-binding agents, such as paclitaxel (Taxus brevifolia) were originally discovered through robust NCI botanical screenings. In this study, a high-through microarray format was utilized to screen 897 aqueous extracts of commonly used natural products (0.00015–0.5 mg/ml) relative to paclitaxel for anti-mitotic effects (independent of toxicity) on proliferation of MDA-MB-231 cells. The data obtained showed that less than 1.34 % tested showed inhibitory growth (IG50) properties <0.0183 mg/ml. The most potent anti-mitotics (independent of toxicity) were Mandrake root (Podophyllum peltatum), Truja Twigs (Thuja occidentalis), Colorado desert mistletoe (Phoradendron flavescens), Tou Gu Cao Speranskia Herb (Speranskia tuberculata), Bentonite Clay, Bunge Root (Pulsatilla chinensis), Brucea Fruit (Brucea javanica), Madder Root (Rubia tinctorum), Gallnut of Chinese Sumac (Melaphis chinensis), Elecampane Root (Inula Helenium), Yuan Zhi Root (Polygala tenuifolia), Pagoda Tree Fruit (Melia Toosendan), Stone Root (Collinsonia Canadensis) and others such as American Witchhazel, Arjun and Bladderwrack. The strongest tumoricidal herbs identified from amongst the subset evaluated for anti-mitotic properties were wild yam (Dioscorea villosa), beth-root (Trillium Pendulum) and alkanet-root (Lithospermum canescens). Additional data was obtained on a lesser-recognized herb: (Speranskia tuberculata) which showed growth inhibition on BT-474 (human ductal breast carcinoma) and Ishikawa (human endometrial adenocarcinoma) cells with ability to block replicative DNA synthesis leading to G2 arrest in MDA-MB-231 cells. In conclusion, these findings present relative potency of natural anti-mitotic resources effective against human breast carcinoma MDA-MB-231 cell division.

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Section: Discussionmentioning

confidence: 99%

High Throughput Screening of Natural Products for Anti‐mitotic Effects in MDA‐MB‐231 Human Breast Carcinoma Cells

Mazzio

Badisa

Mack

et al. 2013

Phytotherapy Research

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“…23 Brusatol (Bru), a quassinoid isolated from the Chinese herbal medicine Brucea javanica fruit, 24 demonstrates various bioactivities, including anticancer. 25 Moreover, Bru can improve chemotherapy efficiency by inhibiting the up-expression of nuclear factor erythroid 2-related factor 2, 26 which contributes to chemoresistance. 27,28 However, like numerous other anticancer candidates, its high hydrophobicity caused by the multiple hydrophobic rings in the molecular structure greatly limits clinical application through intravenous administration.…”

Section: Introductionmentioning

confidence: 99%

Redox-sensitive micelles composed of disulfide-linked Pluronic-linoleic acid for enhanced anticancer efficiency of brusatol

Zhang¹,

Fang²,

Li³

et al. 2018

IJN

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Brusatol (Bru) exhibits promising anticancer effects, with both proliferation inhibition and chemoresistance amelioration activity. However, the poor solubility and insufficient intracellular delivery of Bru greatly restrict its application. Herein, to simultaneously utilize the advantages of Pluronics as drug carriers and tumor microenvironment-responsive drug release profiles, a flexible amphiphilic copolymer with a polymer skeleton, that is, Pluronic ® F68 grafting with linoleic acid moieties by redox-reducible disulfide bonds (F68-SS-LA), was synthesized. After characterization by 1 H-nuclear magnetic resonance and Fourier transform infrared spectroscopy, the redox-sensitive F68-SS-LA micelles were self-assembled in a much lower critical micelle concentration than that of the unmodified F68 copolymer. Bru was loaded in micelles (Bru/SS-M) with high loading efficiency, narrow size distribution, and excellent storage stability. The redox-sensitive Bru/SS-M exhibited rapid particle dissociation and drug release in response to a redox environment. Based on the enhanced cellular internalization, Bru/SS-M achieved higher cytotoxicity in both Bel-7402 and MCF-7 cells compared with free Bru and nonreducible micelles. The improved anticancer effect was attributed to the remarkably decreased mitochondrial membrane potential and increased reactive oxygen species level as well as apoptotic rate. These results demonstrated that F68-SS-LA micelles possess great potential as an efficient delivery vehicle for Bru to promote its anticancer efficiency via an oxidation pathway.

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“…Fructus Bruceae has been used traditionally for the treatment of cancers, malaria and dysenteric disorders, and is known to be a rich source of quassinoids (Wu et al, 2015;Zhao et al, 2011). Bruceine D, a quassinoid, is a chief constituent of Fructus Bruceae (Dong et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a sensitive LC–MS/MS assay for quantification of bruceine D in rat plasma

Zhang

Yong

Zhang

et al. 2016

Biomedical Chromatography

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A sensitive LC-MS/MS method for the determination of bruceine D in rat plasma was developed. The analyte and IS were separated on a Luna C column (2.1 × 50 mm, 1.7 μm) using a mobile phase of acetonitrile and 0.1% formic acid in water (40:60, v/v) at a flow rate of 0.25 mL/min. The selected reaction monitoring mode was chosen to monitor the precursor-to-product ion transitions of m/z 409.2 → 373.2 for bruceine D and m/z 469.2 → 229.3 for IS using a negative ESI mode. The method was validated over a concentration range of 0.5-2000 ng/mL for bruceine D. Total chromatography time for each run was 3.5 min. The method was successfully applied to a pharmacokinetic study of bruceine D in rats. Copyright © 2016 John Wiley & Sons, Ltd.

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Seven Quassinoids from Fructus Bruceae with Cytotoxic Effects on Pancreatic Adenocarcinoma Cell Lines

Cited by 41 publications

References 20 publications

High Throughput Screening of Natural Products for Anti‐mitotic Effects in MDA‐MB‐231 Human Breast Carcinoma Cells

High Throughput Screening of Natural Products for Anti‐mitotic Effects in MDA‐MB‐231 Human Breast Carcinoma Cells

Redox-sensitive micelles composed of disulfide-linked Pluronic-linoleic acid for enhanced anticancer efficiency of brusatol

Development and validation of a sensitive LC–MS/MS assay for quantification of bruceine D in rat plasma

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