Search Results (12)

Chalcones, potential anticancer agents, have shown promise in the suppression of multidrug resistance due to the inhibition of drug efflux driven by certain adenosine triphosphate (ATP)-binding cassette (ABC) transporters. The gene and protein expression of chosen ABC transporters (multidrug resistance protein 1, ABCB1; multidrug resistance-associated protein 1, ABCC1; and breast cancer resistance protein, ABCG2) in human colorectal cancer cells (COLO 205 and COLO 320, which overexpress active ABCB1) was mainly studied in this work under the influence of a novel synthetic acridine-based chalcone, 1C. While gene expression dropped just at 24 h, compound 1C selectively suppressed colorectal cancer cell growth and greatly lowered ABCB1 protein levels in COLO 320 cells at 24, 48, and 72 h. It also reduced ABCC1 protein levels after 48 h. Molecular docking and ATPase tests show that 1C probably acts as an allosteric modulator of ABCB1. It also lowered galectin-1 (GAL1) expression in COLO 205 cells at 24 h. Functional tests on COLO cells revealed ABCB1 and ABCC1/2 to be major contributors to multidrug resistance in both. Overall, 1C transiently lowered GAL1 in COLO 205 while affecting important functional ABC transporters, mostly ABCB1 and to a lesser extent ABCC1 in COLO 320 cells. COLO 320’s absence of GAL1 expression points to a possible yet unknown interaction between GAL1 and ABCB1. Full article

Ribosome-inactivating proteins (RIPs) are a group of proteins with rRNA N-glycosylase activity that irreversibly inhibit protein synthesis and consequently cause cell death. Recently, an RIP called ledodin has been found in shiitake; it is cytotoxic, strongly inhibits protein synthesis, and shows rRNA N-glycosylase activity. In this work, we isolated and characterized a 50 kDa cytotoxic protein from shiitake that we named edodin. Edodin inhibits protein synthesis in a mammalian cell-free system, but not in insect-, yeast-, and bacteria-derived systems. It exhibits rRNA N-glycosylase and DNA-nicking activities, which relate it to plant RIPs. It was also shown to be toxic to HeLa and COLO 320 cells. Its structure is not related to other RIPs found in plants, bacteria, or fungi, but, instead, it presents the characteristic structure of the fold type I of pyridoxal phosphate-dependent enzymes. Homologous sequences have been found in other fungi of the class Agaricomycetes; thus, edodin could be a new type of toxin present in many fungi, some of them edible, which makes them of great interest in health, both for their involvement in food safety and for their potential biomedical and biotechnological applications. Full article

Indonesia is among the countries with the most significant biodiversity globally. Jamu, the traditional medicine of Indonesia, predominantly uses herbal materials and is an integral component of the Indonesian healthcare system. The present study reviewed the ethnobotanical data of seven Indonesian Euphorbiaceae species, namely Euphorbia atoto, E. hypericifolia, Homalanthus giganteus, Macaranga tanarius, Mallotus mollissimus, M. rufidulus, and Shirakiopsis indica, based on the RISTOJA database and other literature sources. An antimicrobial screening of the plant extracts was performed in 15 microorganisms using the disk diffusion and broth microdilution methods, and the antiproliferative effects were examined in drug-sensitive Colo 205 and resistant Colo 320 cells by the MTT assay. The antimicrobial testing showed a high potency of M. tanarius, H. giganteus, M. rufidulus, S. indica, and E. atoto extracts (MIC = 12.5–500 µg/mL) against different bacteria. In the antitumour screening, remarkable activities (IC₅₀ 0.23–2.60 µg/mL) were demonstrated for the extracts of H. giganteus, M. rufidulus, S. indica, and E. atoto against Colo 205 cells. The n-hexane extract of E. atoto, with an IC₅₀ value of 0.24 ± 0.06 µg/mL (Colo 205), was subjected to multistep chromatographic separation, and 24-methylene-cycloartan-3β-ol, jolkinolide E, tetra-tert-butyl-diphenyl ether, α-tocopherol, and β-sitosterol were isolated. Full article

Polyporenic acids N-R (1–5), five novel 24-methylene lanostane triterpenes along with seven known polyporenic acids (6–12), were identified from the fruiting bodies of Buglossoporus quercinus. The isolation of compounds 1–12 was performed by a combination of multistep flash chromatography and reversed-phase high-performance liquid chromatography (HPLC). The structure determination was carried out by extensive spectroscopic analysis, including 1D and 2D nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) experiments. The isolated fungal metabolites were investigated for their antiproliferative activity in vitro by 3-(4,5-dimethylthiazol2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on the resistant Colo 320 human colon adenocarcinoma cell line expressing P-glycoprotein (ABCB1). The lanostane triterpenes exerted moderate antiproliferative activity with IC₅₀ values in the range of 20.7–106.2 μM. A P-glycoprotein efflux pump modulatory test on resistant Colo 320 cells highlighted that fungal metabolites 3, 5, 8, and 10–12 have the ability to inhibit the efflux pump activity of cancer cells. Moreover, the drug interactions of triterpenes with doxorubicin were studied by the checkerboard method. Compounds 3–4, and 7–12 interacted in a synergistic manner, while an outstanding potency was detected for compound 9, which was defined as strong synergism (CI = 0.276). The current study reveals that B. quercinus is a remarkable source of fungal steroids with considerable chemosensitizing activity on cancer cells. Full article

Multidrug resistance (MDR) is a major challenge in cancer chemotherapy. Aiming at generating a small library of anticancer compounds for overcoming MDR, lycorine (1), a major Amaryllidaceae alkaloid isolated from Pancratium maritimum, was derivatized. Thirty-one new compounds (2–32) were obtained by chemical transformation of the hydroxyl groups of lycorine into mono- and di-carbamates. Compounds 1–32 were evaluated as MDR reversers, through the rhodamine-123 accumulation assay by flow cytometry and chemosensitivity assays, in resistant human colon adenocarcinoma cancer cells (Colo 320), overexpressing P-glycoprotein (P-gp, ABCB1). Significant inhibition of P-gp efflux activity was observed for the di-carbamate derivatives, mainly those containing aromatic substituents, at non-cytotoxic concentrations. Compound 5, bearing a benzyl substituent, and compounds 9 and 25, with phenethyl moieties, were among the most active, exhibiting strong inhibition at 2 µM, being more active than verapamil at 10-fold higher concentration. In drug combination assays, most compounds were able to synergize doxorubicin. Moreover, some derivatives showed a selective antiproliferative effect toward resistant cells, having a collateral sensitivity effect. In the ATPase assay, selected compounds (2, 5, 9, 19, 25, and 26) were shown to behave as inhibitors. Full article

Pholiols L-S (1–8), eight undescribed triterpenes were isolated from the sporocarps of the mushroom Pholiota populnea. Various chromatographic techniques, such as open column chromatography, flash chromatography, gel filtration, preparative thin layer chromatography, and HPLC, were applied to purify the compounds. The structure elucidation was carried out by spectroscopic analysis, including 1D (¹H NMR and ¹³C JMOD) and 2D NMR (¹H-¹H COSY, HSQC, HMBC and NOESY) and HRESIMS experiments. The isolated compounds had lanostane (1–7) or trinorlanostane (8) skeletons; all of them were substituted with 3-hydroxy-3-methylglutaroyl group or its 6-methyl ester. Five compounds (1, 2, 4, 6, and 8) were investigated for their antiproliferative and cytotoxic activity in vitro by MTT assay on breast cancer (MCF-7), human colon adenocarcinoma (sensitive Colo 205, and resistant Colo 320), non-small cell lung cancer (A549), and human embryonic lung fibroblast (MRC-5) cell lines. Pholiols M (2) and O (4) showed antiproliferative activity against the MCF-7 cell line with IC₅₀ of 2.48 and 9.95 µM, respectively. These compounds displayed tumor cell selectivity on MCF-7 cells with SI values of >40 (2) and 4.3 (4), but they did not show a cytotoxic effect, proving their action exclusively on tumor cell proliferation. Pholiols L (1) and Q (8) were found to have selective cytotoxicity on drug resistant cells in comparison to their effects on Colo320 and Colo205 cells [relative resistance values 0.84 (1) and 0.62 (8)]. Full article

Ribosome-inactivating proteins (RIPs) are known as RNA N-glycosylases. They depurinate the major rRNA, damaging ribosomes and inhibiting protein synthesis. Here, new single-chain (type-1) RIPs named sodins were isolated from the seeds (five proteins), edible leaves (one protein) and roots (one protein) of Salsola soda L. Sodins are able to release Endo’s fragment when incubated with rabbit and yeast ribosomes and inhibit protein synthesis in cell-free systems (IC₅₀ = 4.83–79.31 pM). In addition, sodin 5, the major form isolated from seeds, as well as sodin eL and sodin R, isolated from edible leaves and roots, respectively, display polynucleotide:adenosine glycosylase activity and are cytotoxic towards the Hela and COLO 320 cell lines (IC₅₀ = 0.41–1200 nM), inducing apoptosis. The further characterization of sodin 5 reveals that this enzyme shows a secondary structure similar to other type-1 RIPs and a higher melting temperature (Tm = 76.03 ± 0.30 °C) and is non-glycosylated, as other sodins are. Finally, we proved that sodin 5 possesses antifungal activity against Penicillium digitatum. Full article

Globally, colon cancer is a major cause of deaths, being the fourth most common type of cancer in the world. The most common therapeutic choice in the early stages of colon cancer is surgical resection, but in some stages of the disease, adjuvant chemotherapy is recommended and is essential for the proper treatment of this pathology [¹]. Complex combinations based on metals play an important role in the treatment of cancer because of their cytotoxic properties against cancer cells. An organometallic compound that can be used clinically and that plays an important role in the treatment of patients with colon cancer is oxaliplatin. Following studies, chlorine-based derivatives of Au (I)-phosphate showed comparable values to cisplatin on HT-29 (colon cancer) cell lines. Further studies continued to determine absorption at the cellular level, showing that most lipophilic compounds demonstrated a higher colon cancer cell absorption, meaning that they could be correlated with high antiproliferative activity [²]. Copper-based complex combinations were studied, and an inhibitory effect in the nanomolar range on the Colo 205 and Colo 320 colon cancer cell lines was thus observed. Some complexes showed increased toxicity to cancer cells compared to the MRC-5 cell lines. The antiproliferative activity of these complex combinations is significantly low in normal cell lines, thus increasing selectivity towards neoplastic cells was observed. Complex combinations based on Cu (I) show cytotoxic effects against LoVo MDR cell lines that are five times higher compared to oxaliplatin, thus showing the ability to overcome oxaliplatin resistance [³]. Nanostructured drug delivery systems allow the incorporation of metal-based drugs, thus limiting some of their most common shortcomings, such as low selectivity, low solubility and permeability, and high toxicity, which limit he dosage and the emergence of resistance at the cellular level [⁴]. These drug delivery systems are able to carry the drug and to release it according to its requested dose, even in a targeted manner, thus improving therapeutic activity and limiting systemic toxicity. Full article

Phenanthrenes are the main special metabolites of Juncaceae species from phytochemical, pharmacological, and chemotaxonomical points of view. The present study focused on the isolation, structure determination, and pharmacological investigation of phenanthrenes from Juncus ensifolius. Nineteen compounds, including 17 phenanthrenes, were identified from the methanol extract of the plant. Thirteen compounds, namely, ensifolins A–M (1–13), were obtained for the first time from natural sources. Four phenanthrenes [2-hydroxy-1,7-dimethyl-5-vinyl-9,10-dihydrophenanthrene (14), juncuenin B (15), juncatrin B (16), and sylvaticin A (17)], 4-hydroxybenzaldehyde (18) and luteolin (19) were isolated for the first time from J. ensifolius. Ensifolins A (1) and B (2) are structurally unique phenanthrenes, considering that they are flavonoid- (1) or benzaldehyde-adducts (2). The antiproliferative activity of all isolated compounds against HeLa, COLO 205, and COLO 320 cancer cells and a non-tumor (MRC-5) cell line was tested using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) viability assay. The luteolin-substituted phenanthrene ensifolin A (1) proved to be the most active against all three cancer cell lines (IC₅₀ values 3.9–12.7 μM) and showed good selectivity (SI = 4.95) in the case of COLO 205. The best selectivity was recorded for ensifolins D (4, SI > 5.15, HeLa), H (8, SI > 8.13, HeLa), and 17 (SI > 9.43, HeLa). The synergistic activity of the compounds with doxorubicin was also tested on HeLa cells, and ensifolins E (5) and H (8) exhibited very strong synergism (CI < 0.1). In conclusion, these phenanthrenes are worthy of further investigation. Full article

Investigation of the methanol extract of the poroid fungus Fuscoporia torulosa resulted in the isolation of a novel triterpene, fuscoporic acid (1), together with inoscavin A and its previously undescribed Z isomer (2 and 3), 3,4-dihydroxy-benzaldehide (4), osmundacetone (5), senexdiolic acid (6), natalic acid (7), and ergosta-7,22-diene-3-one (8). The structures of fungal compounds were determined on the basis of NMR and MS spectroscopic analyses, as well as molecular modeling studies. Compounds 1, 6–8 were examined for their antibacterial properties on resistant clinical isolates, and cytotoxic activity on human colon adenocarcinoma cell lines. Compound 8 was effective against Colo 205 (IC₅₀ 11.65 ± 1.67 µM), Colo 320 (IC₅₀ 8.43 ± 1.1 µM) and MRC-5 (IC₅₀ 7.92 ± 1.42 µM) cell lines. Potentially synergistic relationship was investigated between 8 and doxorubicin, which revealed a synergism between the examined compounds with a combination index (CI) at the 50% growth inhibition dose (ED₅₀) of 0.521 ± 0.15. Several compounds (1 and 6–8) were tested for P-glycoprotein modulatory effect in Colo 320 resistant cancer cells, but none of the compounds proved to be effective in this assay. Fungal metabolites 2–5 were evaluated for their antioxidant activity using the oxygen radical absorbance capacity (ORAC) and DPPH assays. Compounds 4 and 5 were found to have a considerable antioxidant effect with EC₅₀ 0.25 ± 0.01 (DPPH) and 12.20 ± 0.92 mmol TE/g (ORAC). The current article provides valuable information on both the chemical and pharmacological profiles of Fuscoporia torulosa, paving the way for future studies with this species. Full article

Sakuranetin belongs to the group of methoxylated flavanones. It is widely distributed in Polyomnia fruticosa and rice, where it acts as a phytoalexin. Other natural sources of this compound are, among others, grass trees, shrubs, flowering plants, cheery, and some herbal drugs, where it has been found in the form of glycosides (mainly sakuranin). Sakuranetin has antiproliferative activity against human cell lines typical for B16BL6 melanoma, esophageal squamous cell carcinoma (ESCC) and colon cancer (Colo 320). Moreover, sakuranetin shows antiviral activity towards human rhinovirus 3 and influenza B virus and was reported to have antioxidant, antimicrobial, antiinflammatory, antiparasitic, antimutagenic, and antiallergic properties. The aim of this review is to present the current status of knowledge of pro-health properties of sakuranetin. Full article

Medicinal herbs are being increasingly recognized as useful complementary treatments for cancer. Colon cancer is the third most common cancer in men and the second in women worldwide. Colon cancer diseases is very heterogeneous in terms of grade, genetics, ploidy, and oncogene/tumor suppress or gene expression and its biological, hormonal, and molecular characteristics are extremely complex. In this study our aim was to identify the effect of different medical plants Viscum album, Inula viscosa, Hypericum perforatum, Lysimachia nummularia, Oleocanthal, Pinus pinaster and Rubus caeisus on colon cancer cell line. Colo320 cancer cells and human adipose tissue derived mesenchymal stem cell were analysed for four medical plants in culture. Firstly, the cytotoxicity rate (IC50) determined by MTT. After that, immunocytochemical staining were done eNOS, VEGF and TUNEL method for apoptosis. The stainings were evaluated by H-score. As a result, Inula viscosa and Rubus caeisus have a higher inhibitory effect on cell proliferation and apoptosis in both cancers than the other medicinal plants. Colo320 cancer cells expressed strong eNOS by these plants and also both plants were not toxic for adipose tissue derived mesenchymal stem cells. Full article