Dataset Information

A novel triterpenoid isolated from the root bark of Ailanthus excelsa Roxb (Tree of Heaven), AECHL-1 as a potential anti-cancer agent.

ABSTRACT:

Background

We report here the isolation and characterization of a new compound Ailanthus excelsa chloroform extract-1 (AECHL-1) (C(29)H(36)O(10); molecular weight 543.8) from the root bark of Ailanthus excelsa Roxb. The compound possesses anti-cancer activity against a variety of cancer cell lines of different origin.

Principal findings

AECHL-1 treatment for 12 to 48 hr inhibited cell proliferation and induced death in B16F10, MDA-MB-231, MCF-7, and PC3 cells with minimum growth inhibition in normal HEK 293. The antitumor effect of AECHL-1 was comparable with that of the conventional antitumor drugs paclitaxel and cisplatin. AECHL-1-induced growth inhibition was associated with S/G(2)-M arrests in MDA-MB-231, MCF-7, and PC3 cells and a G(1) arrest in B16F10 cells. We observed microtubule disruption in MCF-7 cells treated with AECHL-1 in vitro. Compared with control, subcutaneous injection of AECHL-1 to the sites of tumor of mouse melanoma B16F10 implanted in C57BL/6 mice and human breast cancer MCF-7 cells in athymic nude mice resulted in significant decrease in tumor volume. In B16F10 tumors, AECHL-1 at 50 microg/mouse/day dose for 15 days resulted in increased expression of tumor suppressor proteins P53/p21, reduction in the expression of the oncogene c-Myc, and downregulation of cyclin D1 and cdk4. Additionally, AECHL-1 treatment resulted in the phosphorylation of p53 at serine 15 in B16F10 tumors, which seems to exhibit p53-dependent growth inhibitory responses.

Conclusions

The present data demonstrate the activity of a triterpenoid AECHL-1 which possess a broad spectrum of activity against cancer cells. We propose here that AECHL-1 is a futuristic anti-cancer drug whose therapeutic potential needs to be widely explored for chemotherapy against cancer.

SUBMITTER: Lavhale MS

PROVIDER: S-EPMC2671403 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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A novel triterpenoid isolated from the root bark of Ailanthus excelsa Roxb (Tree of Heaven), AECHL-1 as a potential anti-cancer agent.

Lavhale Manish S MS Kumar Santosh S Mishra Shri Hari SH Sitasawad Sandhya L SL

PloS one 20090428 4

<h4>Background</h4>We report here the isolation and characterization of a new compound Ailanthus excelsa chloroform extract-1 (AECHL-1) (C(29)H(36)O(10); molecular weight 543.8) from the root bark of Ailanthus excelsa Roxb. The compound possesses anti-cancer activity against a variety of cancer cell lines of different origin.<h4>Principal findings</h4>AECHL-1 treatment for 12 to 48 hr inhibited cell proliferation and induced death in B16F10, MDA-MB-231, MCF-7, and PC3 cells with minimum growth i ...[more]

PMID: 19399188

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Project description:This study aimed to assess the phytochemical composition, in vitro antioxidant, cytotoxicity, and in vivo anti-inflammatory activities of the methanolic extract of Ailanthus excelsa (Simaroubaceae) stem bark and its fractions. Quantitative phytochemical analysis revealed that methanolic extract and all fractions contained a high level of flavonoids (20.40-22.91 mg/g QE), phenolics (1.72-7.41 mg/g GAE), saponins (33.28-51.87 mg/g DE), and alkaloids (0.21-0.33 mg/g AE). The antioxidant potential was evaluated in vitro using a range of assays, i.e., DPPH•, ABTS radical scavenging ability, and total antioxidant capacity. The chloroform and ethyl acetate fractions showed stronger antioxidant activity than the methanol extract. In vitro cytotoxic activity was investigated in three human tumor cell lines (A-549, MCF7 and HepG2) using the SRB assay. In addition, the in vivo anti-inflammatory effect was assessed by carrageenan-induced paw edema in rats. The chloroform fraction showed a more pronounced effect by effectively controlling the growth with the lowest GI50 and TGI concentrations. The human lung cancer cell line (A-549) was found to be more sensitive to the chloroform fraction. Furthermore, the chloroform fraction exhibited significant anti-inflammatory activity at a dose of 200 mg/kg in the latter phase of inflammation. Besides, methanol extract and ethyl acetate fraction revealed a significant cytotoxic and anti-inflammatory effects. The chloroform fraction of stem bark showed a strong anti-inflammatory effect in experimental animals and significant COX-2 inhibitory potential in the in vitro experiments. GC-MS analysis of chloroform fraction identified the phytochemicals like caftaric acid, 3,4-dihydroxy phenylacetic acid, arachidonic acid, cinnamic acid, 3-hydroxyphenylvaleric acid, caffeic acid, hexadeconoic acid, and oleanolic acid. The in-silico results suggest that identified compounds have better affinity towards the selected targets, viz. the BAX protein (PDB ID: 1F16), p53-binding protein Mdm-2 (PDB ID: 1YCR), and topoisomerase II (PDB ID: 1QZR). Amongst all, caftaric acid exhibited the best binding affinity for all three targets. Thus, it can be concluded that caftaric acid in combination with other phenolic compounds, might be responsible for the studied activity. Additional in vivo and in vitro studies are required to establish their exact molecular mechanisms and consider them as lead molecules in developing of valuable drugs for treating oxidative stress-induced disorders, cancers, and inflammations.

Project description:Dietary change influenced the life-history traits, nutritional utilization, and midgut serine proteinases in the larvae of the domesticated polyphagous S. ricini, transferred from R. communis (common name: castor; family Euphorbiaceae; the host plant implicated in its domestication) to A. excelsa (common name: Indian tree of heaven; family Simaroubaceae; an ancestral host of wild Samia species). Significantly higher values for fecundity and body weight were observed in larvae feeding on R. communis (Scr diet), and they took less time to reach pupation than insects feeding on A. excelsa (Scai diet). Nevertheless, the nutritional index for efficiency of conversion of digested matter (ECD) was similar for larvae feeding on the two plant species, suggesting the physiological adaptation of S. ricini (especially older instars) to an A. excelsa diet. In vitro protease assays and gelatinolytic zymograms using diagnostic substrates and protease inhibitors revealed significantly elevated levels (p ≤ 0.05) of digestive trypsins, which may be associated with the metabolic costs influencing slow growth in larvae feeding on A. excelsa. RT-PCR with semidegenerate serine proteinase gene-specific primers, and cloning and sequencing of 3' cDNA ends identified a large gene family comprising at least two groups of putative chymotrypsins (i.e., Sr I and Sr II) resembling invertebrate brachyurins/collagenases with wide substrate specificities, and five groups of putative trypsins (i.e., Sr III, Sr IV, Sr V, Sr VII, and Sr VIII). Quantitative RT-PCR indicated that transcripts belonging to the Sr I, Sr III, Sr IV, and Sr V groups, especially the Sr IV group (resembling achelase I from Lonomia achelous), were expressed differentially in the midguts of fourth instars reared on the two plant species. Sequence similarity indicated shared lineages with lepidopteran orthologs associated with expression in the gut, protein digestion, and phytophagy. The results obtained are discussed in the context of larval serine proteinases in dietary adaptations, domestication, and exploration of new host plant species for commercial rearing of S. ricini.

Dataset Information

A novel triterpenoid isolated from the root bark of Ailanthus excelsa Roxb (Tree of Heaven), AECHL-1 as a potential anti-cancer agent.

Background

Principal findings

Conclusions

Publications

A novel triterpenoid isolated from the root bark of Ailanthus excelsa Roxb (Tree of Heaven), AECHL-1 as a potential anti-cancer agent.

Similar Datasets

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