Use of the in Vivo Hollow Fiber Assay in Natural Products Anticancer Drug Discovery

Mi, Qiuwen; Pezzuto, John M.; Farnsworth, Norman R.; Wani, Mansukh C.; Kinghorn, A. Douglas; Swanson, Steven M.

doi:10.1021/np800767a

Cited by 59 publications

(78 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the cost of the traditional xenograft assay is high, and it takes a substantial period of time due to the large number of animals required. The in vivo HFA in immunodeficient nude mice was designed at the NCI to try to bridge the gap between in vitro cell-based assays and human tumor models; the goal of the assay was to predict which compounds would be active in a subsequent xenograft system (56)(57)(58)(59). In the HFA, proliferating cancer cells containing hollow fibers with pores, which are small enough to retain the cancer cells, but large enough to permit potential chemotherapeutic drugs to enter, are transplanted into the peritoneum or under the skin of the host mice.…”

Section: Discussionmentioning

confidence: 99%

“…In the HFA, proliferating cancer cells containing hollow fibers with pores, which are small enough to retain the cancer cells, but large enough to permit potential chemotherapeutic drugs to enter, are transplanted into the peritoneum or under the skin of the host mice. Next, test drug candidates are administered to the mice, and the fibers are then retrieved for analysis of any viable cell masses (56). The HFA is similar to the xenograft assay, but is a time-and cost-saving method.…”

Section: Discussionmentioning

confidence: 99%

“…Proteins were then loaded in equal amounts (20 Hollow fiber assay (HFA). An HFA was performed fol lowi ng t he st a nd a rd p ro c e du r es s et by t he National Cancer Institute (NCI; Bethesda, MD, USA; https://dtp.cancer.gov/branches/btb/hfa.html) (39)(40)(41)(42). Briefly, the two tumor cell lines, A549 and HepG2, were cultured in 75-cm 2 culture flasks.…”

Section: Flow Cytometric Analysismentioning

confidence: 99%

See 2 more Smart Citations

A potential oral anticancer drug candidate, Moringa oleifera leaf extract, induces the apoptosis of human hepatocellular carcinoma cells

2015

View full text Add to dashboard Cite

Abstract. It has previously been reported that cold water-extracts of Moringa oleifera leaf have anticancer activity against various human cancer cell lines, including non-small cell lung cancer. In the present study, the anticancer activity of M. oleifera leaf extracts was investigated in human hepatocellular carcinoma HepG2 cells. By the analysis of apoptotic signals, including the induction of caspase or poly(ADP-ribose) polymerase cleavage, and the Annexin V and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assays, it was demonstrated that M. oleifera leaf extracts induce the apoptosis of HepG2 cells. In the hollow fiber assay, oral administration of the leaf extracts significantly reduced (44-52%) the proliferation of the HepG2 cells and A549 non-small cell lung cancer cells. These results support the potential of soluble extracts of M. oleifera leaf as orally administered therapeutics for the treatment of human liver and lung cancers.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Flow Cytometric Analysismentioning

confidence: 99%

See 1 more Smart Citation

A potential oral anticancer drug candidate, Moringa oleifera leaf extract, induces the apoptosis of human hepatocellular carcinoma cells

2015

View full text Add to dashboard Cite

show abstract

“…This method may be used as a secondary discriminator to prioritize compounds possessing promising in vitro activity for potential further testing in a relevant in vivo xenograft model. [29][30][31][32] The human cancer cell lines evaluated using ip administration comprised MDA-MB-435 (melanoma), MCF-7 (breast), and HT-29 (colon) for the in vivo hollow fiber assay. However, no inhibition of proliferation by 3 was observed over the course of the study for any of the cancer cell types, which were administrated at a dose range of 0.5 to 10 mg /kg/day.…”

Section: Resultsmentioning

confidence: 99%

Isolation, structure elucidation, and biological evaluation of 16,23-epoxycucurbitacin constituents from Eleaocarpus chinensis

Li¹,

Yong²,

Deng³

et al. 2012

Planta Med

View full text Add to dashboard Cite

Eight new 16,23-epoxycucurbitacin derivatives, designated as elaeocarpucins A-H (1-8), and five known cucurbitacins (9-13) were isolated from the chloroform-soluble partitions of separate methanol extracts of the fruits and stem bark of Elaeocarpus chinensis collected in Vietnam. Isolation work was facilitated using a LC/MS dereplication procedure, and bioassay-guided fractionation was monitored using HT-29 human cancer cells. The structures of compounds 1-8 were determined on the basis of spectroscopic data interpretation, with the absolute configurations of isomers 1 and 2 established by the Mosher ester method. Compounds 1-13 were evaluated in vitro against the HT-29 cell line and using a mitochondrial transmembrane potential assay. Elaeocarpucin C (3), produced by partial synthesis from 16α,23α-epoxy-3β,20β-dihydroxy-10αH, 23βH-cucurbit-5,24-dien-11-one (13), was found to be inactive when evaluated in an in vivo hollow fiber assay using three different cancer cell types (dose range 0.5-10 mg/kg/day, ip).Elaeocarpus chinensis (Gardner & Champ.) Hook.f. ex Benth. (syn.: Friesia chinensis Gardner & Champ.), an evergreen tree of the family Elaeocarpaceae, is distributed mainly in subtropical or tropical areas of Asia, including southern mainland China, Laos, and Vietnam. 1 Besides being grown for ornamental purposes, E. chinensis is used also as a traditional Chinese herbal medicine for the treatment of emmeniopathy as well as * Corresponding Author, Tel: +1-614-247-8094. Fax: +1-614-247-8119. kinghorn@pharmacy.ohio-state.edu. # Dedicated to Dr. Gordon M. Cragg, formerly of the National Cancer Institute, Frederick, Maryland, for his pioneering work on the development of natural product anticancer agents.ASSOCIATED CONTENT Supporting Information. 1 H, 13 C and 2D NMR spectra of compounds 1-8, 1 H NMR of (R)-and (S)-MTPA esters of 1 and 2, and hollow fiber assay data for 3. This material is available free-of-charge via the Internet at http://pubs.acs.org. 28 and 16α,23α-epoxy-3β,20β-dihydroxy-10αH,23βH-cucurbit-5,24-dien-11-one (13). 11 Moreover, from the less potently cytotoxic CHCl 3 extract of the stem bark of the same plant, two additional new cucurbitacins, elaeocarpucins G (7) and H (8), were purified. Herein, we report the isolation and structure elucidation of the eight new compounds, 1-8, as well as the biological assessment of all isolates obtained in this investigation. -3β,20β-dihydroxy-10αH,23βH-cucurbit-5,24-dien-11-one (13), a known 16α,23α-epoxycucurbitane analogue first isolated from Eleaocarpus hainanensis 9 that was also identified in the present investigation. Comparison of the 1D-and 2D-NMR data of 1 with those of 13 revealed a major change evident in the side chain located at C-23, with a 2-methylprop-1-ene group in 13 being replaced by a 2-methylprop-2-en-1-ol moiety in 1. C-27) in the 13 C NMR spectrum. Moreover, key HMBC correlations from the terminal olefinic methylene protons of H-27 to C-24, C-25, and C-26, as well as H-24 and H-26 to C-27, supported the structure assigned ...

show abstract

“…The purpose is to identify synthetic compounds or natural products that show selective growth inhibition or cell killing activity, in particular tumor cell lines, and then to perform further evaluations of these compounds. Among the 60 cell lines in the screen, 12 were selected for the Hollow Fiber assay (8) eter) polyvinylidene fluoride hollow fibers with a molecular weight exclusion of 500 kDa. Three different tumor lines are prepared for each experiment and each mouse receives 3 intra-peritoneal implants (1 from each tumor line).…”

Section: Early Drug Discoverymentioning

confidence: 99%

A new paradigm for cancer therapeutics development

Kim¹

2010

BMB Reports

View full text Add to dashboard Cite

The number of cancer patients has increased due to longer life spans and treatment has become a universal problem. Since molecular-targeted therapies were introduced as a new developmental strategy, certain targets have been examined hundreds of times, with developers overlapping their research efforts. We need to focus our energy and resources on novel drug candidate identification and optimization, in order to enhance the entry of early-stage drug candidates into the therapeutics pipeline. This presents a major opportunity for Korea to jump the decades-old development gap between our programs and those that are more advanced in other countries. Although this country does not have a specific center for validation and development of cancer therapeutics, we do have cutting-edge scientists performing research in many institutions. In this paper, I will review cancer drug development in Korea and suggest future directions, while urging colleagues to utilize their networking expertise so we can move toward a new paradigm of novel therapeutics development. An example of such efforts has begun with the Drug Development Consortium, which was described in the KSBMB chapter. This consortium was launched in 2010 by biochemists, chemists, cell and molecular biologists and pharmacologists. It is clear that effective cancer therapeutics will be developed more efficiently when we all strive for the same goal. [BMB reports 2010; 43(6): 383-388]

show abstract

Use of the in Vivo Hollow Fiber Assay in Natural Products Anticancer Drug Discovery

Cited by 59 publications

References 79 publications

A potential oral anticancer drug candidate, Moringa oleifera leaf extract, induces the apoptosis of human hepatocellular carcinoma cells

A potential oral anticancer drug candidate, Moringa oleifera leaf extract, induces the apoptosis of human hepatocellular carcinoma cells

Isolation, structure elucidation, and biological evaluation of 16,23-epoxycucurbitacin constituents from Eleaocarpus chinensis

A new paradigm for cancer therapeutics development

Contact Info

Product

Resources

About