Cytotoxic activity of polyacetylenes and polyenes isolated from roots of Echinacea pallida

Abstract

Background and purpose: The n-hexane extracts of the roots of three medicinally used Echinacea species exhibited cytotoxic activity on human cancer cell lines, with Echinacea pallida found to be the most cytotoxic. Acetylenes are present in E. pallida lipophilic extracts but essentially absent in extracts from the other two species. In the present study, the cytotoxic effects of five compounds, two polyacetylenes (namely, 8-hydroxy-pentadeca-(9E)-ene-11,13-diyn-2-one (1) and pentadeca-(9E)-ene-11,13-diyne-2,8-dione (3)) and three polyenes (namely, 8-hydroxy-pentadeca-(9E,13Z)-dien-11-yn-2-one (2), pentadeca-(9E,13Z)-dien-11-yne-2,8-dione (4) and pentadeca-(8Z,13Z)-dien-11-yn-2-one (5)), isolated from the n-hexane extract of E. pallida roots by bioassay-guided fractionation, were investigated and the potential bioavailability of these compounds in the extract was studied. Experimental approach: Cytotoxic effects were assessed on human pancreatic MIA PaCa-2 and colonic COLO320 cancer cell lines. Cell viability was evaluated by the WST-1 assay and apoptotic cell death by the cytosolic internucleosomal DNA enrichment and the caspase 3/7 activity tests. Caco-2 cell monolayers were used to assess the potential bioavailability of the acetylenes. Key results: The five compounds exhibited concentration-dependent cytotoxicity in both cell types, with a greater potency in the colonic cancer cells. Apoptotic cell death was found to be involved in the cytotoxic effect of the most active, compound 5. Compounds 2 and 5 were found to cross the Caco-2 monolayer with apparent permeabilities above 10 Â 10 À6 cm s À1 . Conclusions and implications: Compounds isolated from n-hexane extracts of E. pallida roots have a direct cytotoxicity on cancer cells and good potential for absorption in humans when taken orally.

Bauer ketones 23 and 24 from Echinacea paradoxa var. paradoxa inhibit lipopolysaccharide-induced nitric oxide, prostaglandin E2 and cytokines in RAW264.7 mouse macrophages

“…Apart from its anti-inflammatory activity, Bauer ketone 24 (compound 2) from E. pallida has also been reported to inhibit the growth of human cancer cell lines possibly by arresting the cell cycle in the G1 phase and promoting apoptotic cell death (Chicca et al, 2010). Bauer ketone 24 (compound 2) is evidently permeable above 10 × 10 −6 cms −1 across the Caco-2 monolayer, suggesting potential oral bioavailability (Chicca et al, 2008). Therefore, Bauer ketone 24 (compound 2) might be a promising candidate as an anti-inflammatory and anti-tumor agent.…”

“…Anti-inflammatory activity has been observed with a polysaccharide fraction and with polyunsaturated alkamides from E. angustifolia roots, and echinacoside, alkamides and polyenes/polyacetylenes from E. pallida (LaLone et al, 2007; LaLone et al, 2009; Tubaro et al, 1987). In addition, polyenes and polyacetylenes from E. pallida roots have also been reported to induce apoptosis of tumor cells (Chicca et al, 2008). …”

The use of natural products in colorectal cancer drug discovery

“…Reyes-Zurita et al found that maslinic acid induces apoptosis in HT29 colon cancer cells via the mitochondrial apoptotic pathway [69]. Furthermore, NPs with other structures, such as polyacetylenes and polyenes [72], chromane derivatives [73], grifolin [74], g-oryzanol [75], yuanhuacine [76], chartreusin [77] and statins [78], have been explored for the purpose of drug discovery for CRC ( Table 5). In addition, NPs derived from organisms in marine environments have recently been investigated.…”

“…Honokiol [65], magnolol [66], podophyllotoxin, silibinin, hydnocarpin Substances other than polyphenols Alkaloids Antofine [67,68], avenanthramide, neo-clerodane diterpenoid alkaloids, taspine Terpenes Maslinic acid [69], talaporfin, novel triterpenoids, ent-clerodane diterpenoids, curcuphenol, picrotoxin, solaniol, triptolide, carnosic acid, koetjapic acid, andrographolide, plaunotol, geranylgeraniol Sapogenin Yerba mate tea and mate saponins [70], Paris saponin VII [71] Other substances Polyacetylenes and polyenes [72], chromane derivatives [73], grifolin [74], g-oryzanol [75], yuanhuacine [76], chartreusin [77], simvastatin and lovastatin [78], TPU942 and its derivatives [79], PTZ0025, phytic acid, b-sitosterol, diallyl sulfide, brefeldin A, parthenolide, norcantharidin, protopanaxadiol, melanoidin, evodiamine, 1'-acetoxychavicol acetate, panaxadiol, renieramycin, pyrazolone derivatives, b-asarone, phthalide, turmerone…”

Cytotoxic Activity and Secondary Metabolite Characteristics of Sea Cucumber Actinopyga sp. Methanolic Extract

“…Crude extract from natural product is considered as having strong cytotoxic activity if the LC 50 value is under 30 mg/ml (Munro et al, 1987;Suffnes & Pezzuto, 1990;Itharat et al, 2004;Chicca et al, 2008). Based on this criterion, the methanolic crude extract of sea cucumber Actinopyga sp.…”