Antiproliferative and cytotoxic activities of Mentha x piperita L. essential oil in non-small cell lung cancer cells

Among 33 types of listed cancers worldwide, lung cancer with 2.2 million cases (12.2% of total cancer cases) ranks second next only to breast cancer. Globally, Turkey, with overall rate of 40.0 (41,264 cases), ranks 5th among top 10 countries in lung cancer. Currently used therapeutic agents and approaches have considerable side effects, and hence, there is a need for alternative agents for effective management of lung cancer. In this study, we explored the in vitro cytotoxic, antiproliferative and proapoptotic activities of Mentha x piperita L. (peppermint) essential oil in human non-small cell lung cancer (A549) cells. Cell viability was determined by MTT assay, morphological changes were determined by confocal microscopy and apoptosis promoting action was determined by flow cytometry technique. Peppermint essential oil found to effectively decrease the viability of non-small cell lung cancer cells and IC50 value was detected at low concentrations (2.12%) for 24 h. In addition, peppermint essential oil was found to alter the morphology of A549 cells, leading to changes that could describe programmed cell death. Apoptosis was the triggered cell death by Mentha x piperita essential oil. Results reveal that Mentha x piperita essential oil has antiproliferative and anticarcinogenic properties which could be attributed to the bioactive phytochemical contents and has the potential to be used as an anticancer agent and chemotherapeutic drug.

Nitrate reduction in Haloferax alexandrinus: the case of assimilatory nitrate reductase

Haloferax alexandrinus Strain TM JCM 10717T = IFO 16590T is an extreme halophilic archaeon able to produce significant amounts of canthaxanthin. Its genome sequence has been analysed in this work using bioinformatics tools available at Expasy in order to look for genes encoding nitrate reductase-like proteins: respiratory nitrate reductase (Nar) and/or assimilatory nitrate reductase (Nas). The ability of the cells to reduce nitrate under aerobic conditions was tested. The enzyme in charge of nitrate reduction under aerobic conditions (Nas) has been purified and characterised. It is a monomeric enzyme (72 ± 1.8 kDa) that requires high salt concentration for stability and activity. The optimum pH value for activity was 9.5. Effectiveness of different substrates, electron donors, cofactors and inhibitors was also reported. High nitrite concentrations were detected within the culture media during aerobic/microaerobic cells growth. The main conclusion from the results is that this haloarchaeon reduces nitrate aerobically thanks to Nas and may induce denitrification under anaerobic/microaerobic conditions using nitrate as electron acceptor. The study sheds light on the role played by haloarchaea in the biogeochemical cycle of nitrogen, paying special attention to nitrate reduction processes. Besides, it provides useful information for future attempts on microecological and biotechnological implications of haloarchaeal nitrate reductases.This work was funded by research grant from the MINECO Spain (CTM2013-43147-R) and by funds from the Department of Biology, Faculty of Science, Anadolu University (Turkey)

Promising anti-growth effects of palladium(II) saccharinate complex of terpyridine by inducing apoptosis on transformed fibroblasts in vitro

Fibrosarcoma is one of the fatal cancer types and there is still not satisfactory success in its treatment despite new drugs. Therefore, the search for a new compound has been going on. It is currently known that some palladium-based anti-cancer compounds seem to have powerful apoptosis-inducing effects in cancer cells. For this purpose, a palladium(II)-saccharinate complex containing terpyridine which was synthesized by our research group was investigated in terms of its anti-tumor effects against mouse embryonic fibroblast NIH/3T3 (normal cell line) and rat embryonic fibroblast 5RP7 (H-ras transformed cell line) in vitro. The MTT and ATP viability assays were used to determine anti-growth/cytotoxic effects. Cytotoxic activity was confirmed by real time cytotoxicity analysis system. Flow cytometry analysis was further used to determine the mode of cell death (apoptosis/necrosis). Apoptosis was confirmed by triple-staining the cells with Hoechst 33342/PI/Calcein-AM triple and evaluated with fluorescence microscopy. It was found that the compound showed significant anti-growth activity by inducing apoptosis in a dose dependent manner. In conclusion, taking into account the cytotoxic activity of the compound at even relatively lower doses, in vivo experiments to elucidate its potential use for the treatment of fibrosarcoma are warranted.Anadolu Üniversitesi (1110F164

TİTANYUM DİOKSİTİN A549 HÜCRELERİ ÜZERİNDEKİ APOPTOTİK ETKİLERİ

Metal temelli bileşikler potansiyel etkilerinden ve az toksisiteye neden olduklarından dolayı uzun zamandır kullanılmaktadır. Metal bileşik sisplatin çeşitli kanser türlerine karşı tıbbi olarak kullanılmış ve yan etkiler göstermiştir. Biz bu çalışmada sisplatine alternatif ajan olarak düşündüğümüz titanyum dioksitin A549 hücreleri üzerindeki etkilerini ve apoptotik mekanizmasını araştırdık. Titanyum dioksitin 24, 48 ve 72 saatlik sürelerdeki zamana ve konsantrasyon aralığına bağlı olarak antiproliferatif etkilerini MTT canlılık analizini kullanarak belirledik. Titanyum dioksitin apoptozisi tetiklediğini saptadık. Titanyum dioksitin IC30 konsantrasyonu, 72 saat süresince A549 hücreleri üzerinde uygulandığında erken ve geç apoptozisi tetiklediği belirlendi. Titanyum dioksitin IC30 konsantrasyonu, 72 saat süresince A549 hücreleri üzerine uygulandığında mitokondriyal membran potansiyelini azaltarak apoptozisi tetikledi. Buna rağmen kaspaz-3 aktivitesi gözlenmedi. Titanyum dioksit kaspazdan bağımsız bir yol izleyerek apoptozisi tetiklemiştir diyebiliriz. Titanyum dioksitin IC30 konsantrasyonun 72 saatlik süre sonundaki hematoksilen ve eozin, TUNEL, BrdU, Bcl-2 ve Bax immünositokimyasal analizleri sonucunda  apoptotik indekslerinde artış belirlendi. Titanyum dioksitin IC30 konsantrasyonun uygulandığı A549 hücrelerinde 72 saatlik süre sonunda konfokal ve TEM mikrokobisi kullanılarak çeşitli apoptotik yapılar gözlendi. Bu sonuçlar titanyum dioksitin A549 hücreleri üzerinde antiproliferatif ve apoptotik etkilerini ve sisplatine eş potansiyel kemoterapötik bir ajan olabileceğini göstermektedir

Protective effects of ellagic acid in D-galactosamine-induced kidney damage in rats

D-Galactosamine (D-GalN), which is an established experimental toxin, primarily causes liver injury by the generation of free radicals and depletion of UTP nucleotides. D-GalN intoxication also induces renal dysfunction thus, renal failure is often associated with the end-stage of the liver damage. We have investigated both preventive and curative effects of ellagic acid (EA) in this study. EA treatment at a gavage dose of 20 mg/kg body weight was administered before and after intraperitoneal (i.p.) injection of D-GalN at a dose of 750 mg/kg. Tissue and blood samples of animals were collected for morphological and biochemical evaluations. Our study results suggest that EA treatment both prior to and after the toxin administration successfully altered the toxic effects on the rats. Moreover, pre-treatment of EA was more protective than post-treatment indicated by histopathological and biochemical values. In conclusion, EA treatment both before and after D-GalN intoxication could protect kidney tissues against D-GalN induced oxidative stress

Potential therapeutic effects of silymarin and silymarin-loaded solid lipid nanoparticles on experimental kidney damage in BALB/c mice: biochemical and histopathological evaluation

Silymarin (Sm) is widely used in treating diseases that affect organs such as the liver, kidney, and gallbladder thanks to its antioxidative, renoprotective, antihepatotoxic, and anticarcinogenic properties. However, this substance is poorly solved in water and tends to decompose in the intestine, its bioavailability decreasing before it can show real effect. With these limitations in mind, the present study aims to enhance the poor bioavailability of Sm by forming Sm-loaded solid lipid nanoparticles (Sm-SLNs) using the hot homogenization method. A characterization process was undertaken to determine possible impact of Sm on experimental kidney damage. Our biochemical and light microscopic results suggest that the group that received Sm-SLNs for the treatment of D-GalN/ TNF-?–induced experimental kidney damage showed significantly more improvement than the group that received commercially available Sm. In conclusion, Sm-loaded SLN may be a useful system for the delivery of poorly water-soluble Sm and may also provide renoprotection.Anadolu University Scientific Research Project Unit (project no.: 1305F091)

A comparative study on the therapeutic effects of silymarin and silymarin-loaded solid lipid nanoparticles on D-GaIN/TNF-?-induced liver damage in Balb/c Mice

Nanostructure mediated drug delivery is known to have a potential to improve drug bioavailability, apart from fostering release deviation of drug molecules and enabling precision drug targeting. Solid lipid nanoparticles (SLNs) have drawn great deal of the attention of scientists in ?nding a solution to minimize pharmaceutic limitations of the drugs used. Silymarin(Sm)has so far been used for treating diverse liver and gall bladder disorders, such as cirrhosis, hepatitis, and jaundice, and for protecting the liver against poisoning from chemical and environmental toxins on account of its antihepatotoxic and antioxidative properties. The present study aims to develop a novel silymarin-loaded solid lipid nanoparticle (SmloadedSLN) system with enhanced bioavailability and with an ability to provide excellent hepatic protection for poorly water-soluble drugs. Based upon our investigation results with apoptotic markers, PCNA and light microscopic ?ndings, it can be concluded that Sm-loaded SLN signi?cantly reduced D-GaIN/TNF?-induced hepatotoxicity, which suggested improved bioactivity compared to Sm. In conclusion, Sm-loaded SLN could be a useful system for the delivery of poorly water-soluble Sm, apart from providing favourable hepatic protection

Antiproliferative and cytotoxic activities of Mentha x piperita L. essential oil in non-small cell lung cancer cells

753-758Among 33 types of listed cancers worldwide, lung cancer with 2.2 million cases (12.2% of total cancer cases) ranks second next only to breast cancer. Globally, Turkey, with overall rate of 40.0 (41,264 cases), ranks 5th among the top 10 countries in lung cancer. Currently used therapeutic agents and approaches have considerable side effects, and hence, there is a need for alternative agents for effective management of lung cancer. In this study, we explored the in vitro cytotoxic, antiproliferative and proapoptotic activities of Mentha x piperita L. (peppermint) essential oil in human non-small cell lung cancer (A549) cells. Cell viability was determined by MTT assay, morphological changes were determined by confocal microscopy and apoptosis promoting action was determined by flow cytometry technique. Peppermint essential oil found to effectively decrease the viability of non-small cell lung cancer cells and IC50 value was detected at low concentrations (2.12%) for 24 h. In addition, peppermint essential oil was found to alter the morphology of A549 cells, leading to changes that could describe programmed cell death. Apoptosis was the triggered cell death by Mentha x piperita essential oil. Results reveal that Mentha x piperita essential oil has antiproliferative and anticarcinogenic properties which could be attributed to the bioactive phytochemical contents and has the potential to be used as an anticancer agent and chemotherapeutic drug