Anticancer, antioxidant, and antibacterial activity of chemically fingerprinted extract from Cyclamen persicum Mill.

In the last few decades, researchers have thoroughly studied the use of plants in Palestine, one of them is Cyclamen persicum Mill. (C. persicum). Cyclamen persicum has been historically cultivated since the 1700s due to its tuber. The tuber is known to stimulate the nasal receptors, thus triggering the sensory neurons. Cyclamen persicum has anti-inflammatory effects, reduces cholesterol levels, treats diabetes, and inhibits tumor growth. In this respect, in-vitro examination of antibacterial and anticancer activities and antioxidative potency of C. persicum ethanolic extract were evaluated. The antioxidative potency of the extracted plant material was determined spectrophotometrically using the DPPH free radical scavenging method and the HPLC-PDA method to evaluate its total phenolic content (TPC) and total flavonoid content (TFC). The experimental results revealed weak antibacterial activity of C. persicum extract against both gram negative (E. coli) and gram positive (Streptococcus aureus and S. aureus) bacterial strains, with the zones of inhibition found to be less than 8 mm. On the other hand, powerful activity against MCF7 breast cancer as well as HT29 colon cancer cell lines was obtained. The findings also revealed potent inhibition of free radicals and the presence of maximal levels of natural products such as phenolic compounds and flavonoids, which supportits biological activities and powerful ability to scavenge free radicals. HPLC results showed the presence of numerous flavonoid and phenolic compounds such as rutin, chlorogenic acid, kaempferol, trans-cinnamic acid, quercetin, sinapic acid, and p-coumaric acid.

Advances in the Transformation of Cyclamen persicum Mill. Through Direct Regeneration Based on an Optimized Kanamycin Selection Scheme.

Gene transfer technology has great value in ornamental plants toward the generation of varieties with new ornate characteristics. In the previous studies through the transformation of cyclamen, hygromycin was mainly used as a selective marker. However, there have been some drawbacks associated with hygromycin usage as a selecting agent. Therefore, in the current study, the optimization of kanamycin concentration in the regeneration media has been considered. Subsequently, the plant transformation using three different in vitro explants from three Cyclamen persicum cultivars using three Agrobacterium tumefaciens strains has been examined. Accordingly, the optimal kanamycin concentrations for regeneration from root and leaf explants were determined as 10 mg/L and for microtuber explants as 30 mg/L. The successful gene transformation in the antibiotic-resistant shoots were examined by PCR and UV-equipped microscopes. The gfp reporter gene transfer resulted in the highest efficiency of transformation (60%) to date, from the leaf explants of cv. Pure White inoculated with Agrobacterium tumefaciens strain LBA4404. In contrast, the lowest gene transfer efficiency (25%) was observed in root explants of cv. Dark Violet and cv. Neon Pink inoculated with strains GV3101 and AGL-1, respectively. The results of the current project are expandable to the subsequent investigations of Cyclamen persicum transformation.

Insights into chloroplast genome structure, intraspecific variation, and phylogeny of Cyclamen species (Myrsinoideae).

Species from the flowering plant genus Cyclamen are popular amongst consumers. In particular Cyclamen persicum Mill. has been significantly used commercially, and certain small flowering species such as Cyclamen hederifolium and Cyclamen coum are gradually growing in popularity in the potted flower market. Here, the chloroplast genomes of nine Cyclamen samples including four Cyclamen species and five varieties of C. hederifolium were sequenced for genome structure comparison, White green septal striped leaves related gene screening and DNA molecular markers were developed for phylogenetic analysis. In comparing Cyclamen species' chloroplast genomes, gene content and gene order were found to be highly similar with the length of genomes ranging from 151,626 to 153,058 bp. The chloroplast genome of Cyclamen has 128 genes, including 84 protein-coding genes, 36 transfer RNA genes, and 8 ribosomal RNA genes. Based on intraspecific variation, seven hotspots, including three genes and four intergenic regions, were identified as variable markers for downstream species delimitation and interspecific relationship analyses. Moreover, a phylogenetic tree constructed with complete chloroplast genomes, revealed that Cyclamen are monophyletic with Lysimachia as the closest neighbor. Phylogenetic analyses of the 14 Cyclamen species with the seven variable regions showed five distinct clades within this genus. The highly supported topologies showed these seven regions may be used as candidate DNA barcode sequences to distinguish Cyclamen species. White green septal striped leaves is common in C. hederifolium, however the molecular mechanism of this has not yet been described. Here, we find that the intergenic region rps4-trnT-UGU seems related to white green septal striped leaves.

Comparative anatomical survey of Cyclamen L. (Primulaceae) taxa and their traditional medicinal uses in Turkey.

The genus Cyclamen is native to Turkey, where it is represented by 12 perennial tuberous geophytic taxa. In this study, a detailed anatomical description of all Cyclamen taxa found in Turkey is provided for the first time. Tuber, root, petiole, and leaf cross-sections were stained with Astra blue and safranin, and tuber slides were also stained with sartur. Tubers of these taxa used by local people as a treatment for infertility were separately investigated. Stomatal index values and epidermis cell features of the studied taxa were measured. Indumentum features of the leaves were described for the first time. Petiole and leaf anatomy and particularly stomatal density, size, and index, provided valuable evidence for species identification. Although the anatomical features of these taxa are not sufficient as diagnostic characters, they can be used together with morphological features.

Occupational rhinoconjunctivitis to cyclamen: A case report / Rinoconjuntivite ocupacional a cyclamen - Caso clínico

Cyclamen is a plant belonging to the Primulaceae family, widely used as an indoor ornamental flowering plant. Occupational allergy to cyclamen has been occasionally described in the current literature. The authors intend to report the case and diagnostic approach of a suspected occupational cyclamen allergy.

O ciclame é uma planta pertencente à família Primulaceae, amplamente utilizada como planta ornamental de interior. A alergia ocupacional ao ciclame raramente foi descrita na literatura. Os autores pretendem descrever um caso e abordagem diagnóstica de uma suspeita de alergia ocupacional ao ciclame.

Chemical characterization, antioxidant, enzyme inhibitory and cytotoxic properties of two geophytes: Crocus pallasii and Cyclamen cilicium.

The Crocus and Cyclamen genus have been reported to possess diverse biological properties. In the present investigation, two geophytes from these genus, namely Crocus pallasi and Cyclamen cilicium have been studied. The in vitro antioxidant, enzyme inhibitory, and cytotoxic effects of the methanol extracts of Crocus pallasii and Cyclamen cilicium aerial and underground parts were investigated. Antioxidant abilities of the extracts were investigated via different antioxidant assays (metal chelating, radical quenching (ABTS and DPPH), reducing power (CUPRAC and FRAP) and phosphomolybdenum). Cholinesterases, amylase, tyrosinase, and glucosidase were used as target enzymes for detecting enzyme inhibitory abilities of the samples. Regarding the cytotoxic abilities, breast cancer cell lines (MDA-MB 231 and MCF-7) and prostate cancer cell lines (DU-145) were used. The flowers extracts of Crocus pallasii and C. cilicium possessed the highest flavonoid content. The highest phenolic content was recorded from C. cilicium root extract (47.62 mg gallic acid equivalent/g extract). Cyclamen cilicium root extract showed significantly (p < 0.05) high radical scavenging (94.28 and 139.60 mg trolox equivalent [TE]/g extract, against DPPH and ABTS radicals, respectively) and reducing potential (173.30 and 109.53 mg TE/g extract, against CUPRAC and FRAP, respectively). The best acetylcholinesterase, glucosidase and tyrosinase inhibition was observed in C. cilicium root (4.46 mg GALAE/g; 15.75 mmol ACAE/g; 136.99 mg KAE/g, respectively). Methanolic extracts of C. pallasii and C. cilicium showed toxicity against breast cancer cell lines. In light of the above findings, C. cilicium might be considered as an interesting candidate in the development of anti-cancer agent coupled with antioxidant properties.

Intranasal immunization of guinea pig with trivalent influenza antigen adjuvanted by Cyclamen europaeum tubers extract.

Cyclamen europaeum tubers extract (CTE) with concentration commonly used for human rhinosinusitis treatment was tested as mucosal adjuvant in experimental intranasal immunization of guinea pigs with concentrated commercially available influenza trivalent vaccine and subsequent infection with influenza strain A/California/04/2009 H1N1pdm. Dual intranasal immunization with vaccine compound consisting of 7.5 µg of each hemagglutinin and 500 µg of CTE in 50 µl induced reciprocal GMT on day 21 after immunization 40 (5-640) against H1N1pdm; 43.20 (5-1280) against H3N2; 10.80 (5-80) against influenza B. Animals with HI titers 1/80 against cell-derived antigen were completely protected against challenge with A/California/04/2009 H1N1pdm09.

High-Throughput Sequencing Reveals Cyclamen persicum Mill. as a Natural Host for Fig Mosaic Virus.

In a search for viral infections, double-stranded RNA (dsRNA) were recovered from a diseased cyclamen (Cyclamen persicum Mill.) accession (Cic) and analyzed by high-throughput sequencing (HTS) technology. Analysis of the HTS data showed the presence of Fig mosaic emaravirus (FMV) in this accession. The complete sequences of six FMV-Cic RNA genomic segments were determined from the HTS data and using Sanger sequencing. All FMV-Cic RNA segments are similar in size to those of FMV from fig (FMV-Gr10), with the exception of RNA-6 that is one nucleotide longer. The occurrence of FMV in cyclamen was investigated through a small-scale survey, from which four plants (out of 18 tested) were found RT-PCR positive. To study sequence variations of cyclamen isolates of FMV, RT-PCR products generated through the amplification of the partially RNA-dependent RNA polymerase (RdRp, RNA-1), glycoprotein (GP, RNA-2), and nucleocapsid (NCP, RNA-3) genes were explored. The nucleotide sequence identities for cyclamen isolates ranged between 86% and 99% in RNA-1, 93% and 99% in RNA-2, and 98% and 99% in RNA-3, while lower identity levels were observed with the sequences of fig isolates. Based on the phylogenetic tree obtained with a 304-nt fragment of RNA3, all FMV isolates from cyclamens were assigned to a single cluster close to fig isolates from the Mediterranean. FMV was graft-transmitted to healthy cyclamens eliciting symptoms similar to those observed in the Cic accession, thus suggesting a causal role of FMV in the symptoms that prompted the investigation. This is the first report of FMV in a non-fig host, Cyclamen persicum, a finding that may help in the control of the mosaic and mosaic-like diseases of fig and cyclamen, respectively.

Cyclamen europaeum improves the effect of oral antibiotics on exacerbations and recurrences of chronic rhinosinusitis: a real-life observational study (CHRONOS).

SUMMARY: Chronic rhinosinusitis (CRS) is an inflammatory disease of the nose and paranasal sinuses affecting 11% of the European population. Cyclamen europaeum plant extract (CE) has demonstrated efficacy in treating acute rhinosinusitis, but its role in CRS exacerbations remains unknown. In this real-life, prospective, epidemiological, observational study, a total of 317 patients with exacerbations of CRS without nasal polyps (CRSsNP) of moderate severity were treated using three different options: oral antibiotics, CE extract nasal spray, or the combination of oral antibiotic with CE extract. The main outcomes were the effect of treatment on sinonasal symptoms and endoscopic appearance after 6 weeks of therapy, and the number of recurrences of CRS exacerbations after 6 months of follow-up. On the top of oral antibiotics, CE extract significantly improved sinonasal symptoms and endoscopic findings and caused a 4-fold reduction of CRS recurrences. When administered in monotherapy, CE extract was at least as effective as antibiotic in monotherapy on relief of both symptoms and reduction of CRS recurrences. In patients with CRS exacerbation of moderate severity, CE extract nasal spray in monotherapy or added to standard antibiotic treatment significantly reduces sinonasal symptoms and CRS recurrences compared to antibiotics in monotherapy.

Cyclamen europaeum extract for acute sinusitis.

BACKGROUND: Acute sinusitis is a common reason for primary care encounters. It causes significant symptoms including facial pain, congested nose, headache, thick nasal mucus, fever, and cough and often results in time off work or school. Sinusitis treatment focuses on eliminating causative factors and controlling the inflammatory and infectious components. The frozen, dried, natural fluid extract of the Cyclamen europaeum plant delivered intranasally is thought to have beneficial effects in relieving congestion by facilitating nasal drainage, and has an anti-inflammatory effect. OBJECTIVES: To assess the effectiveness of topical intranasal Cyclamen europaeum extract on clinical response in adults and children with acute sinusitis. SEARCH METHODS: We searched CENTRAL, which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE, Embase, and trials registers (ClinicalTrials.gov; WHO ICTRP) in January 2018. We also searched the reference lists of included studies and review literature for further relevant studies and contacted trial authors for additional information. SELECTION CRITERIA: Randomised controlled trials comparing Cyclamen europaeum extract administered intranasally to placebo, antibiotics, intranasal corticosteroids, or no treatment in adults or children, or both, with acute sinusitis. Acute sinusitis was defined by clinical diagnosis and confirmed by nasal endoscopy or by radiological evidence. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included two randomised controlled trials that involved a total of 147 adult outpatients with acute sinusitis confirmed by radiology or nasal endoscopy who were assigned to Cyclamen europaeum nasal spray or placebo study arms for up to 15 days. The risk of selection and detection bias was unclear, as allocation concealment and blinding of outcome assessors were not reported in either study. Attrition was high (60%) in one study, although dropouts were balanced between study arms.Neither study reported our two primary outcomes: proportion of participants whose symptoms resolved or improved at 14 days and 30 days. No serious adverse events or complications related to treatment were reported; however, more mild adverse events such as nasal and throat irritation, mild epistaxis, and sneezing occurred in Cyclamen europaeum group participants (50%) compared to placebo group participants (24%) (risk ratio 2.11, 95% confidence interval 1.35 to 3.29); moderate-quality evidence. AUTHORS' CONCLUSIONS: The effectiveness of Cyclamen europaeum for people with acute sinusitis is unknown. Although no serious side effects were observed, 50% of participants who received Cyclamen europaeum reported adverse events compared with 24% of those who received placebo.

Anti-invasive effect of Cyclamen pseudibericum extract on A549 non-small cell lung carcinoma cells via inhibition of ZEB1 mediated by miR-200c.

Scientists are increasingly focusing attention on natural products of plant origin for use as agents in cancer protection and treatment. Cyclamen L. tuber extracts contain saponin glycosides that have been shown to have anti-cancer and other biological activities. The epithelial-to-mesenchymal transition (EMT) is thought to enhance malignant tumour progress. The transcriptional repressor zinc-finger E-box binding homeobox 1 (ZEB1) is an important inducer of EMT in different human tumours and has recently been shown to boost invasion by tumour cells. In this study, we investigated the effects of endemic Cyclamen pseudibericum (CP) saponin-rich tuber extract on the capacity of non-small cell lung cancer line A549 cells to proliferate, invade and migrate and also examined the expression levels of several invasion-migration-related microRNAs (miRNAs) to identify those which directly targeted ZEB1. The cytotoxicity effect of the CP extract on the A549 cancer cells was determined by the luminometric method. The half-minimal (50%) inhibitory concentration dose in the A549 cells was determined to be 41.64 ± 2.35 µg/mL. Using the Matrigel invasion chamber system and the wound healing assay we observed that the CP extract suppressed the invasion and migration capacity of A549 cells, respectively. The expression of miRNAs in A549 cells was evaluated by real-time PCR. Our data showed that overexpression of miRNA miR-200c hindered the EMT by increasing the expression of E-cadherin and decreasing the expression of both N-cadherin and vimentin through the direct targeting of ZEB1. These findings suggest that the saponin-rich tuber extract of CP may have considerable anti-cancer properties in lung cancer. Further studies are required to examine in detail the molecular-based mechanism involved in the EMT process of the extract along with isolation and identification of active saponin components.

Phytochemical screening and antibacterial activity of Cyclamen persicum Mill tuber extracts.

The emerging drug resistance bacteria increased the demand on the discovery of antibiotics from natural sources. This research was aimed to study the antibacterial reactivity; as well as the phytochemicals, of the wild type of Cyclamen persicum, using nine different extraction methods where four solvents (Methanol, Ethanol, Hexane; and Water) were involved with varied extraction periods ranged from 2 up to 10 hours. The antibacterial activity of crude methanol extract (CME) was found as the best method of extraction, with particular emphasis on the method with prolonged extraction time of (10 hrs). The antibacterial activities of produced CME were determined by using agar diffusion method against two of gram-positive bacteria and two gram-negative ones. The CME treated Mueller-Hinton-Agar plates, were exhibited antibacterial effects against the gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis) by showing of inhibition zone after overnight incubation, while nothing was noticed on those of gram negative ones (Pseudomonas aeruginosa and Escherichia coli). These results that proved the antibacterial activity of the Cyclamen persicum tubers were positively tested the Saponin glycosides from plant. In addition to that, methanol solvent could be the useful method for extractions of Cyclamen and can be used in any developing drugs against pathogenic gram positive bacteria.

The conservation significance of natural hybridisation in Mediterranean plants: from a case study on Cyclamen (Primulaceae) to a general perspective.

Hybridisation plays a prominent role in plant evolution due to its influence on genetic diversity, fitness and adaptive potential. We identify a case of on-going hybrid evolution of floral phenotypes in disjunct populations of Cyclamen balearicum and C. repandum subsp. repandum on Corsica and Sardinia. Hybrid populations on the two islands contain similar patterns of variation in flower colour and size but are probably at different stages in the evolutionary process of hybridisation, and differences in the frequency of floral types and flower size suggest hybrid vigour that may contribute to the dynamics and maintenance of hybrid forms. In a review of cases of hybridisation in Mediterranean plants we found an equivalent number of cases for the contemporary occurrence of mixed hybrid populations, as there are cases of homoploid hybrid species differentiation. We argue for the development of a conservation strategy for Mediterranean plants that integrates the need to protect not just pure endemic species (some of hybrid origin) but also mixed populations where adaptive variation and new species are evolving due to contemporary hybridisation.

Analysis of Pseudomonas aeruginosa PAO1 Biofilm Protein Profile After Exposure to n-Butanolic Cyclamen coum Extract Alone and in Combination with Ciprofloxacin.

Pseudomonas aeruginosa biofilm-related infections are the major cause of premature death in cystic fibrosis patients. Strategies to induce biofilm dispersal are of interest, because of their potential in preventing biofilm-related infections. Our previous work demonstrated that n-butanolic Cyclamen coum extract with ciprofloxacin could eliminate 1- and 3-day-old P. aeruginosa PAO1 biofilms. To gain new insights into the role of C. coum extract and its synergistic effect with ciprofloxacin in eliminating P. aeruginosa PAO1 biofilms, two-dimensional gel electrophoresis (2-DE) in combination with mass spectrometry-based protein identification were used. Changes in the bacterial protein expression were analyzed when 3-day-old biofilm cells were exposed to the C. coum extract alone and in combination with ciprofloxacin. Proteins involved in alginate biosynthesis, quorum sensing, adaptation/protection, carbohydrate and amino acid metabolism showed a weaker expression in the C. coum extract-ciprofloxacin-treated biofilm cells compared to those in the untreated cells. Interestingly, the proteome of C. coum extract-ciprofloxacin-treated biofilm revealed more resemblance to the planktonic phenotype than to the biofilm phenotype. It appears that saponin extract in combination with ciprofloxacin causes biofilm disruption due to several mechanisms such as motility induction, cell envelope integrity perturbation, stress protein expression reduction, and more importantly, signal transduction perturbation. In conclusion, exposure to a combination of biofilm dispersal such as saponin extract and antimicrobial agents may offer a novel strategy to control preestablished, persistent P. aeruginosa biofilms and biofilm-related infections.

Molecular Characterization of Cyclamen Species Collected from Different Parts of Turkey by RAPD and SRAP Markers.

The genus Cyclamen (family Myrsinaceae) contains about 20 species, most of which occur in the Mediterranean region. Turkey has critically important Cyclamen genetic resources. Molecular characterization of plant materials collected from different regions of Turkey in which Cyclamen species grow naturally, namely Adana, Antalya, Aydin, Mugla, Izmir, Denizli, Kahramanmaras, Osmaniye, Eskisehir, Trabzon, and Rize provinces, was performed using RAPD and SRAP markers. DNA was successfully amplified by 30 RAPD primers and 14 SRAP primer pairs. Among the 470 bands generated by the RAPD primers, 467 were polymorphic. The number of bands detected by a single primer set ranged from 11 to 22 (average of 15.6). The percentage polymorphism was 99.3 % based on the RAPD data. In the SRAP analysis, a total of 216 bands were generated, showing 100 % polymorphism. The number of bands detected by a single primer set ranged from 9 to 22 (average of 15.4). All data were scored and UPGMA dendrograms were constructed with similar results in both marker systems, i.e., different species from nine provinces of Turkey were separated from each other in the dendrograms with the same species being clustered together.

Lyophilized Cyclamen europaeum tuber extract in the treatment of rhinosinusitis.

Nasal and sinus mucositis is a significant health problem associated with significant organizational and financial burden for the health care system. In recent years, several important guidelines and positions of expert groups and scientific associations have been published with regard to the diagnostics and treatment of rhinosinusitis, including European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS 2012) [1] and Polish Standards for the Treatment of Rhinitis (PoSLeNN 2013) [2]. The management of viral and postviral rhinosinusitis involves systemic treatment including administration of plant origin products. The goal of this article is to present the current knowledge on the use of intranasal preparations containing natural saponin fractions from the rhizomes of Alpine cyclamen (Cyclamen europaeum). Saponins contained in the extract of Alpine cyclamen (Cyclamen europaeum) rhizomes are surface-active compounds that reduce the surface tension on the nasal mucosal cells while simultaneously stimulating the trigeminal nerve receptors leading to increased production of seromucous secretion and extensive drainage of the nasal and sinus cavities. The analysis of published studies on the efficacy and safety of intranasal products containing lyophilized extracts from Cyclamen europaeum tuber warrants the conclusion that these products are useful in the management of nasal and sinus mucositis due to their beneficial impact on the course of the treatment of acute rhinosinusitis. When used in patients with acute rhinosinusitis, an intranasal preparation containing lyophilized extracts from Cyclamen europaeum tuber efficiently reduces the symptoms, particularly the feeling of pressure and pain in the face. According to the authors of PROSINUS study, single-agent treatment using Cyclamen europaeum extracts is more efficient (in terms of the percentage of success) than other monotherapy or combination regimens.

The importance of arbuscular mycorrhiza for Cyclamen purpurascens subsp. immaculatum endemic in Slovakia.

At present, there is no relevant information on arbuscular mycorrhiza and the effect of the symbiosis on the growth of wild populations of cyclamens. To fill this gap, two populations of Cyclamen purpurascens subsp. immaculatum, endemic in Nízke Tatry (NT) mountains and Velká Fatra (VF) mountains, Slovakia, were studied in situ as well as in a greenhouse pot experiment. For both populations, mycorrhizal root colonization of native plants was assessed, and mycorrhizal inoculation potential (MIP) of the soils at the two sites was determined in 3 consecutive years. In the greenhouse experiment, the growth response of cyclamens to cross-inoculation with arbuscular mycorrhizal fungi (AMF) was tested: plants from both sites were grown in their native soils and inoculated with a Septoglomus constrictum isolate originating either from the same or from the other plant locality. Although the MIP of soil at the NT site was significantly higher than at the VF site, the level of AMF root colonization of C. purpurascens subsp. immaculatum plants in the field did not significantly differ between the two localities. In the greenhouse experiment, inoculation with AMF generally accelerated cyclamen growth and significantly increased all growth parameters (shoot dry weight, leaf number and area, number of flowers, tuber, and root dry weight) and P uptake. The two populations of C. purpurascens subsp. immaculatum grown in their native soils, however, differed in their response to inoculation. The mycorrhizal growth response of NT plants was one-order higher compared to VF plants, and all their measured growth parameters were stimulated regardless of the fungal isolates' origin. In the VF plants, only the non-native (NT originating) isolate showed a significant positive effect on several growth traits. It can be concluded that mycorrhiza significantly increased fitness of C. purpurascens subsp. immaculatum, despite the differences between plant populations, implying that AMF symbionts should be taken into account in conservation programs of this endemic plant.

In vitro cytotoxic and anticlastogenic activities of saxifragifolin B and cyclamin isolated from Cyclamen persicum and Cyclamen libanoticum.

CONTEXT: The genus Cyclamen L. (Primulaceae) is rich in saponins known to have interesting biological activities. OBJECTIVE: To isolate saxifragifolin B and cyclamin, two triterpene saponins, from Cyclamen libanoticum Hildebr and Cyclamen persicum Mill, and to assess their cytotoxic, clastogenic/aneugenic, and anticlastogenic effects, as well as antioxidant potential. MATERIALS AND METHODS: Saxifragifolin B and cyclamin were tested for their cytotoxicity against SK-BR-3, HT-29, HepG2/3A, NCI-H1299, BXPC-3, 22RV1, and normal DMEM cell lines using WST-1 assay. Their clastogenic/aneugenic activities and anticlastogenic effects against the anticancer drug mitomycin C were assessed by the in vitro micronucleus assay in CHO cells. Their antioxidant capacities were determined using Fe(2+)-chelating and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assays. RESULTS: Both saponins were described for the first time in Cyclamen libanoticum. They showed strong cytotoxic activities against the tested cancer cell lines. Saxifragifolin B was found to be 56- and 37-times more active than mitomycin C against breast adenocarcinoma (SK-BR-3) and lung carcinoma (NCI-H1299), respectively. Also, saxifragifolin B did not induce micronuclei formation and prevented cells from mitomycin C clastogenic effect. Cyclamin induced a significant increase of micronucleated cells after metabolic activation with S9 mix, and did not possess any anticlastogenic activity. Both molecules exhibited low antioxidant activities as compared to reference compounds. DISCUSSION AND CONCLUSIONS: This study showed the remarkable cytotoxic activity of saxifragifolin B, especially against breast adenocarcinoma and lung carcinoma and its chemoprotective activity against mitomycin C. Thus, saxifragifolin B could be suggested as a potential cytotoxic drug with a preventive effect against possible exposures to genotoxic agents.

Cyclamen exerts cytotoxicity in solid tumor cell lines: a step toward new anticancer agents?

Cyclamen coum is a traditional medicinal plant in the Turkey. Its anticancer properties and whether cyclamen extract induces any cytotoxicity in solid cancer cell lines have not been thoroughly investigated previously. Therefore we examined cytotoxic effects on cervical cancer, HeLa, and non small cell lung cancer cell, H1299, lines. Cyclamen extract induced cellular death of both HeLa and H1299 cells in a dose dependent manner. We also analyzed the capacity of cyclamen extract to induce apoptosis by the TUNEL method. Here, we for the first time report that the extract of Cyclamen coum, an endemic plant for Turkey, can induce cytotoxicity via apoptosis in HeLa and H1299 cells. These results imply that cyclamen extract can be further analyzed to potentially find novel anticancer compounds.

Multi-petal cyclamen flowers produced by AGAMOUS chimeric repressor expression.

Cyclamen persicum (cyclamen) is a commercially valuable, winter-blooming perennial plant. We cloned two cyclamen orthologues of AGAMOUS (AG), CpAG1 and CpAG2, which are mainly expressed in the stamen and carpel, respectively. Cyclamen flowers have 5 petals, but expression of a chimeric repressor of CpAG1 (CpAG1-SRDX) caused stamens to convert into petals, resulting in a flower with 10 petals. By contrast, CpAG2-SRDX only caused incomplete formation of stamens and carpels. Expression in Arabidopsis thaliana showed similar effects on flower organ specification. Simultaneous expression of CpAG1-SRDX and CpAG2-SRDX in cyclamen induced rose-like, multi-petal flowers, a potentially valuable trait in commercial ornamental varieties. Expression of CpAG2-SRDX in a cyclamen mutant lacking expression of CpAG1 more effectively produced multi-petal flowers. Here, we controlled the number of petals in cyclamen by simple genetic engineering with a chimeric repressor. This strategy may be applicable useful for other ornamental plants with two distinct AG orthologues.