Comparison of cytotoxic effect of β-cyclodextrin and dextran micelles loaded with doxorubicin in KG-1 cells

زمینه و هدف: آنتراسیکلین ها درمان اصلی لوسمی حاد میلوژنز می باشند، اما استفاده از آن ها به دلیل عوارض جاننی محدود شده است. استفاده از میسل های پلیمری برای دارورسانی هدفمند دوکسوروبیسین توسط گیرنده های فولات برای لوسمی حاد میلوژنز می تواند این عوارض را کاهش دهد. این مطالعه با هدف مقایسه سمیت سلولی میسل های تهیه شده از بتاسیکلودکسترین و دکستران حاوی دوکسوروبیسین بر رده ی سلولی KG-1 انجام شده است. روش بررسی: در این مطالعه تجربی آزمایشگاهی، کونژوگه های رتینوئیک اسید/ سیکلودکسترین/ فولیک اسید و رتینوئیک اسید/ دکستران/ فولیک اسید به روش استریفیکاسیون تهیه شدند. بارگیری دارو در میسل ها به روش انحلال مستقیم انجام شد. نانوذرات میسلی بهینه سازی شده براساس اندازه ذره ای، پتانسیل زتا، اندکس پلی دیسپرسیتی، کارایی بارگیری و کارآیی رهش دوکسوروبیسین انتخاب شدند. جهت مطالعه اثر ممانعت از رشد سلولی بر رده سلولی KG-1 از روش رنگ سنجی MTT استفاده شد. یافته ها: دوکسوروبیسین بارگیری شده در نانو ذرات بهینه تهیه شده از کونژوگه ی رتینوئیک اسید/ سیکلودکسترین/ فولیک اسید در غلظت g/mlµ377/0، دارای اثر ممانعت از رشد سلولی حدود 5/10 برابر دوکسوروبیسین آزاد، 3 برابر دوکسوروبیسین بارگیری شده در میسل های رتینوئیک اسید/ سیکلودکسترین و 3/8 برابر دوکسوروبیسین بارگیری شده در میسل های رتینوئیک اسید/ دکستران/ فولیک اسید بود (05/0>P). دوکسوروبیسین بارگیری شده در نانو ذرات بهینه تهیه شده از کونژوگه رتینوئیک اسید/ دکستران/ فولیک اسید در غلظت g/mlµ377/0، دارای اثر ممانعت از رشد سلولی حدود 3/1 برابر دوکسوروبیسین آزاد و 2/1 برابر دوکسوروبیسین بارگیری شده در میسل های رتینوئیک اسید/ دکستران بود (05/0>P). نتیجه گیری: نانو ذرات تهیه شده از سیکلودکسترین حاوی دوکسوروبیسین اثربخشی بیشتری علیه سلول های سرطانی KG-1 نسبت به نانو ذرات تهیه شده از دکستران حاوی دوکسوروبیسین و داروی آزاد دارد

Investigation of Astragalus honey and propolis extract′s cytotoxic effect on two human cancer cell lines and their oncogen and proapoptotic gene expression profiles

Background: Cancer is one of the major fatal human diseases. Natural products have been used in the treatment of cancer for long time. Bee products including honey and propolis have been introduced for malignancy treatment in recent decades. In this study cytotoxicity of bee products and their effects on the expression of proapoptotic genes have been investigated. Materials and Methods: Cytotoxic effects of Astragalus honey, ethanol extract of propolis and a sugar solution (as control) against HepG2, 5637 and L929 cell lines have been evaluated by the MTT assay. Total RNAs of treated cells were isolated and p53 and Bcl-2 gene expression were evaluated, using real-time PCR. Results: Propolis IC50 values were 58, 30 and 15 μg/ml against L929, HepG2 and 5637, respectively. These values for honey were 3.1%, 2.4% and 1.9%, respectively. Propolis extract has increased the expression of the Bcl-2 gene in all cell lines whereas the honey decreased that significantly (P < 0.05). Also, we found that honey and propolis decreased p53 gene expression in HepG2 and 5637 significantly but not in L929 cells. The sugar solution increased the expression of p53 in two cancer cell lines but no significant changes were observed in the expression of this gene in L929 as normal mouse cell. Conclusion: By downregulation of Bcl-2 expression it could be concluded that the cytotoxicity of honey was more than two fold against tested cancer cells compared with the sugar solution. No significant changes were observed in the expression of p53 in honey-treated cells. Propolis had no significant effect on Bcl-2 and p53 gene expressions (P > 0.05)

Evaluation of cytotoxic effects of several novel tetralin derivatives against Hela, MDA-MB-468, and MCF-7 cancer cells

Background: The inhibitors of the enzymes estrone sulfatase and 17-β-hydroxysteroid dehydrogenase (17-β-HSD) could provide a means of blocking estrogen biosynthesis leading to regression of estrogen-dependent tumors. We evaluated the cytotoxicity of several tetralin derivatives, 2-(4-halo-phenylmethylene)-3,4-dihydronaphthalene-1-ones, as potential inhibitors of these two enzymes, on Hela, MDA-MB-468, and MCF-7 cancer cell lines. Materials and Methods: The cell lines were cultured in RPMI medium and the cytotoxic effect of tested compounds (compounds 1 to 5) was screened at the concentrations of 0.1, 1, and 10 μM either alone or in combination with doxorubicin (100 μM), using MTT assay. The mixtures of cell suspension with solvent (1% DMSO in PBS) and doxorubicin (100 μM) were used as negative and positive controls, respectively. Each concentration of compounds was assayed in four wells and repeated in at least three independent experiments for each cell line. The cytotoxic effect of each particular concentration of tested compounds was expressed as the percent of cell survival. Results: None of the compounds exhibited cytotoxic effect (reduction of cell survival to less than 50%) on tested cell lines. However, statistically significant reduction in cell survival was observed for some compounds against particular cell lines. Among all tested combinations of compounds with doxorubicin against cell lines, only compound 4 at 10 μM concentration showed synergistic cytotoxic effect with doxorubicin against Hela cells. Conclusion: With the exception of compound 2, other tested compounds have potential for further cytotoxicity evaluation. Synthesizing other tetralin derivatives similar to compound 4 and studying their structure-activity relationships (SARs) would be encouraged

Cytotoxic Effects of Iranian Mistletoe Extract on a Panel of Cancer Cells: Cytotoxicity of Mistletoe

Extracts derived from Viscum album have been shown to kill cancer cells in vitro. Some studies have noted that different species of this plant collected from around the world displayed cytotoxic effects in different extents. In the present study, we evaluated the effects of Iranian mistletoe extracts on five cancer cell lines. Plants growing on hornbeam tree (Carpinus betulus) were collected, air-dried and hydroalcoholic (MeOH-H2O with 2% acetic acid) and methanolic extracts were obtained using percolation. Also the plant juice was obtained by pressing. Cytotoxicity of the extracts on a panel of cancer cells (Hela, KB, MDA-MB-468, K562 and MCF- 7) were studied using colorimetric MTT assay. Results showed that plant juice was the most cytotoxic fraction on all cancer cells tested (IC50=0.0316 mg). The IC50 of hydroalcoholic and methanolic extracts were 0.1 and 0.316 mg, respectively. These results suggest that alkaloids and huge compounds like viscotoxin and lectins extracted by press or hydroalcoholic solvents were probably responsible for their cytotoxicity. Results also indicated that Hela cells were more resistant while KB cells were more sensitive to the cytotoxic effects of the extracts. It can be concluded that cytotoxicity of Iranian mistletoe extract on the cell lines tested closely depends on the host tree and extraction methods

Cytotoxicity of Euphorbia macroclada on MDA-MB-468Breast CancerCell Line: Cytotoxicity of Euphorbia macroclada

It has been reported that different species of Euphorbia(Euphorbiaceae) have antitumor activity. Some reports also show that these plants have potential cytotoxic effect against different cell lines. In a program to screen the cytotoxicity of Iranian native plants, Euphorbia macrocladaBoiss. was collected, identified, and the cytotoxic activity of dichloromethane, ethylacetate, methanol extracts, and the plant latex were determined against MDA-MB-468 cell line. Different concentration of extracts and latex were added to 24 h cultured cells and then incubated for 72 h under specific condition (37 °C, 5% CO2). Cell survival was evaluated using MTT assay. The results of this study indicated that, dichloromethane and ethylacetate extracts had cytotoxic effects on cell line, while the methanol extract and latex were not cytotoxic at the tested concentrations. The data from this investigation suggest that the nonpolar extracts of E. macrocladapossess higher cytotoxic activity

Antiproliferative Activity and Apoptosis Induction of Crude Extract and Fractions of Avicennia Marina

Objective(s): Regarding the presence of many active biological constituents in Avicennia marina, the present investigation was carried out to study cytotoxic activity of crude methanol leave extract and column chromatographic fractions of A. marina against MDA-MB 231 cell line (human breast cancer cell) and HEK (Human embryonic kidney cell) line .   Materials and Methods: The anticancer activity of crude methanol extract and sub-fractions were evaluated, using MTT assay. The induction of apoptosis was determined by analyzing DNA fragmentation in breast cancer cells treated with active fraction of crude methanol extract using agarose gel electrophoresis. To investigate molecular mechanism of apoptosis, gene expression levels of p53 and Bcl-2 were measured using quantitative real time PCR. Results: Fraction 10 was the most active fraction and was detected with HPLC as luteolin. The 50% cell cytotoxic concentration (CC50) of crude methanol extract and luteolin was 250 and 28 μg/ml, respectively. This fraction was found to be an apoptotic agent against MDA-MB 231 cells, which leads to causing DNA fragmentation. The mRNA expression level of Bcl-2 and p53 was significantly decreased and increased respectively in cancer cells treated by luteolin. Conclusion: The results suggested that Luteolin isolated from Avicennia marina could probably induce apoptosis on breast cancer cell line by the regulation of p53 and Bcl-2 pathways

Effects of Lactobacillus plantarum A7 with probiotic potential on colon cancer and normal cells proliferation in comparison with a commercial strain

Objective(s): Several beneficial effects have been attributed to the probiotic lactic acid bacteria. It was determined that lactobacilli can exert antiproliferative effects on the various cancer cell lines including colon cancer. Effects of lactic acid bacteria on colon cancer may vary from strain to strain and there is a need to find the new probiotic strains with tumor suppressing properties through         in vitro studies. Materials and Methods: Anti-proliferative activities of heat-killed cells and cell-free supernatants of a native strain of Lactobacillus plantarum A7 and a commercial strain of lactobacillus  rhamnosus GG were assessed on human colon cancer cell lines (Caco-2 and HT-29) and normal cells (L-929), using MTT assay. Cells were seeded at 2×104 cells/mlin 96 well plates and incubated for 24 hr. Then heat-killed cells (OD620: 0.025, 0.0.05, 0.1) and cell-free supernatants of bacteria were added at concentration of 2.5, 5 and 10 mg/ml. After 48 hr incubation MTT (5 mg/ml) was added and the absorbance was measured at 540 nm using ELISA plate reader. Results: Results showed that heat-killed cells and cell-free supernatants of both probiotic strains reduced the growth rate of cancer and normal cells. These results suggested that anti-proliferative effect may not be an exclusive characteris ticwhich is dedicated to officially approved probiotics. Conclusion: L. plantarum A7 could be considered as colon cancer biological product, most likely due to its advantages in significant organic acid production

Scaffold percolative efficiency: in vitro evaluation of the structural criterion for electrospun mats

Fibrous scaffolds of engineered structures can be chosen as promising porous environments when an approved criterion validates their applicability for a specific medical purpose. For such biomaterials, this paper sought to investigate various structural characteristics in order to determine whether they are appropriate descriptors. A number of poly(3-hydroxybutyrate) scaffolds were electrospun; each of which possessed a distinguished architecture when their material and processing conditions were altered. Subsequent culture of mouse fibroblast cells (L929) was carried out to evaluate the cells viability on each scaffold after their attachment for 24 h and proliferation for 48 and 72 h. The scaffolds’ porosity, pores number, pores size and distribution were quantified and none could establish a relationship with the viability results. Virtual reconstruction of the mats introduced an authentic criterion, “Scaffold Percolative Efficiency” (SPE), with which the above descriptors were addressed collectively. It was hypothesized to be able to quantify the efficacy of fibrous scaffolds by considering the integration of porosity and interconnectivity of the pores. There was a correlation of 80% as a good agreement between the SPE values and the spectrophotometer absorbance of viable cells; a viability of more than 350% in comparison to that of the controls

Theoretical design of a new chimeric protein for the treatment of breast cancer

p28 and NRC peptides are two anticancer peptides with various mechanisms have shown to be effective against breast cancer. Therefore, it seems that construction of a chimeric protein containing the two peptides might cause synergistic cytotoxic effects. However, since the two peptides bear opposite charges, production of a chimeric protein in which the two moieties do not intervene each other is difficult. In this study, our goal was to find a suitable peptide linker for the new chimeric protein in a manner that none of the peptides intervene the other’s function. We selected some linkers with different characteristics and lengths and created a small library of the chimeric proteins harboring these linkers. Homology modeling and molecular dynamic simulation revealed that (PA)5P and (EAAAK)3 linkers can separate the p28 and NRC peptides effectively. Thus, the chimeric protein linked with (PA)5P or (EAAAK)3 linkers might show synergistic and stronger anticancer effects than the separate peptide moieties because they could exert their cytotoxic effects freely which is not influenced by the other part