New Insights in the Era of Clinical Biomarkers as Potential Predictors of Systemic Therapy-Induced Cardiotoxicity in Women with Breast Cancer: A Systematic Review.

Cardiotoxicity induced by breast cancer therapies is a potentially serious complication associated with the use of various breast cancer therapies. Prediction and better management of cardiotoxicity in patients receiving chemotherapy is of critical importance. However, the management of cancer therapy-related cardiac dysfunction (CTRCD) lacks clinical evidence and is based on limited clinical studies. AIM: To provide an overview of existing and potentially novel biomarkers that possess a promising predictive value for the early and late onset of CTRCD in the clinical setting. METHODS: A systematic review of published studies searching for promising biomarkers for the prediction of CTRCD in patients with breast cancer was undertaken according to PRISMA guidelines. A search strategy was performed using PubMed, Google Scholar, and Scopus for the period 2013-2023. All subjects were >18 years old, diagnosed with breast cancer, and received breast cancer therapies. RESULTS: The most promising biomarkers that can be used for the development of an alternative risk cardiac stratification plan for the prediction and/or early detection of CTRCD in patients with breast cancer were identified. CONCLUSIONS: We highlighted the new insights associated with the use of currently available biomarkers as a standard of care for the management of CTRCD and identified potentially novel clinical biomarkers that could be further investigated as promising predictors of CTRCD.

Chemical Characterization and Antioxidant Activity of Nine Hypericum Species from Greece.

Hypericum L. comprises about 500 species distributed almost worldwide. Research has mainly focused on H. perforatum with confirmed biological activity on the alleviation of depression symptoms, among others. The compounds responsible for such activity are considered naphthodianthrones and acylphloroglucinols. Other Hypericum species are less studied or not studied, and further research is needed to complete the characterization of the genus. In this study we evaluated the qualitative and quantitative phytochemical profile of nine Hypericum species native to Greece, namely H. perforatum, H. tetrapterum, H. perfoliatum, H. rumeliacum subsp. apollinis, H. vesiculosum, H. cycladicum, H. fragile, H. olympicum and H. delphicum. Qualitative analysis was performed using the LC/Q-TOF/HRMS technique, while quantitative data were calculated with the single point external standard method. Additionally, we estimated the antioxidant activity of the extracts using DPPH and ABTS assays. Three species endemic to Greece (H. cycladicum, H. fragile, H. delphicum) were studied for the first time. Our results indicated that all studied species are rich in secondary metabolites, mainly of the flavonoids family, with strong antioxidant activity.

Origanum majorana Essential Oil-A Review of Its Chemical Profile and Pesticide Activity.

Origanum majorana is a medicinal and aromatic plant that belongs to the Lamiaceae family. It is cultivated in several parts of the world and, due to its splendid aroma and taste, is widely used for culinary purposes and in perfumes. The essential oil of the plant, to which is attributed its aroma, contains many secondary metabolites with valuable biological activity. One of them is the pesticide activity, which has attracted much interest. Given the necessity of replacing synthetic pesticides, essential oils are studied in an attempt to find naturally derived products. Thus, the aim of this review paper is to discuss the chemical profile of O. majorana essential oil and to present data regarding its insecticidal, repellent and fumigant activity. Data were collected from 1992 to 2022. Databases, including PubMed, Google Scholar, ScienceDirect and Scopus, were used for the research, and keywords, including O. majorana, sweet marjoram, essential oil, volatiles, pesticide, insecticide and repellent activity, were used. The results of this review paper indicate that O. majorana essential oil can be an alternative agent to manage pests. However, still, much research should be conducted to evaluate its toxicity against beneficial insects and to ensure its safety for human health.

Cytotoxic Effect of Rosmarinus officinalis Extract on Glioblastoma and Rhabdomyosarcoma Cell Lines.

Rosmarinus officinalis is a well-studied plant, known for its therapeutic properties. However, its biological activity against several diseases is not known in detail. The aim of this study is to present new data regarding the cytotoxic activity of a hydroethanolic extract of Rosmarinus officinalis on glioblastoma (A172) and rhabdomyosarcoma (TE671) cancer cell lines. The chemical composition of the extract is evaluated using liquid chromatography combined with time-of-flight mass spectrometry, alongside its total phenolic content and antioxidant activity. The extract showed a promising time- and dose-dependent cytotoxic activity against both cell lines. The lowest IC50 values for both cell lines were calculated at 72 h after treatment and correspond to 0.249 ± 1.09 mg/mL for TE671 cell line and 0.577 ± 0.98 mg/mL for A172 cell line. The extract presented high phenolic content, equal to 35.65 ± 0.03 mg GAE/g of dry material as well as a strong antioxidant activity. The IC50 values for the antioxidant assays were estimated at 12.8 ± 2.7 µg/mL (DPPH assay) and 6.98 ± 1.9 µg/mL (ABTS assay). The compound detected in abundance was carnosol, a phenolic diterpene, followed by the polyphenol rosmarinic acid, while the presence of phenolic compounds such as rhamnetin glucoside, hesperidin, cirsimaritin was notable. These preliminary results suggest that R. officinalis is a potential, alternative source of bioactive compounds to further examine for abilities against glioblastoma and rhabdomyosarcoma.

Clinical Validation of EndoPredict in Pre-Menopausal Women with ER-Positive, HER2-Negative Primary Breast Cancer.

PURPOSE: The EndoPredict prognostic assay is validated to predict distant recurrence and response to chemotherapy primarily in post-menopausal women with estrogen receptor-positive (ER+), HER2- breast cancer. This study evaluated the performance of EndoPredict in pre-menopausal women. EXPERIMENTAL DESIGN: Tumor samples from 385 pre-menopausal women with ER+, HER2- primary breast cancer (pT1-3, pN0-1) who did not receive chemotherapy in addition to endocrine therapy were tested with EndoPredict to produce a 12-gene EP molecular score and an integrated EPclin score that includes pathologic tumor size and nodal status. Associations of molecular and EPclin scores with 10-year distant recurrence-free survival (DRFS) were evaluated by Cox proportional hazards models and Kaplan-Meier analysis. RESULTS: After a median follow-up of 9.7 years, both the EP molecular score and the molecular-clinicopathologic EPclin score were associated with increased risk of distant recurrence [HR, 1.33; 95% confidence interval (CI), 1.18-1.50; P = 7.2 × 10-6; HR, 3.58; 95% CI, 2.26-5.66; P = 9.8 × 10-8, respectively]. Both scores remained significant after adjusting for clinical factors in multivariate analysis. Patients with low-risk EPclin scores (64.7%) had significantly improved DRFS compared with high-risk patients (HR, 4.61; 95% CI, 1.40-15.17; P = 4.2 × 10-3). At 10 years, patients with low-risk and high-risk EPclin scores had a DRFS of 97% (95% CI, 93%-99%) and 76% (95% CI, 67%-82%), respectively. CONCLUSIONS: The EPclin score is strongly associated with DRFS in pre-menopausal women who received adjuvant endocrine therapy alone. On the basis of these data, pre-menopausal women with EPclin low-risk breast cancer may be treated with endocrine therapy only and safely forgo adjuvant chemotherapy.

An In Vitro Study of Saffron Carotenoids: The Effect of Crocin Extracts and Dimethylcrocetin on Cancer Cell Lines.

Crocus sativus L. has various pharmacological properties, known for over 3600 years. These properties are attributed mainly to biologically active substances, which belong to the terpenoid group and include crocins, picrocrocin and safranal. The aim of the current work was to examine the effects of crocins (CRCs) and their methyl ester derivate dimethylcrocetin (DMCRT) on glioblastoma and rhabdomyosarcoma cell lines, in terms of cytotoxicity and gene expression, implicated in proapoptotic and cell survival pathways. Cell cytotoxicity was assessed with Alamar Blue fluorescence assay after treatment with saffron carotenoids for 24, 48 and 72 h and concentrations ranging from 22.85 to 0.18 mg/mL for CRCs and 11.43 to 0.09 mg/mL for DMCRT. In addition, BAX, BID, BCL2, MYCN, SOD1, and GSTM1 gene expression was studied by qRT-PCR analysis. Both compounds demonstrated cytotoxic effects against glioblastoma and rhabdomyosarcoma cell lines, in a dose- and time-dependent manner. They induced apoptosis, via BAX and BID upregulation, MYCN and BCL-2, SOD1, GSTM1 downregulation. The current research denotes the possible anticancer properties of saffron carotenoids, which are considered safe phytochemicals, already tested in clinical trials for their health promoting properties.

Chemical Characterization, Antioxidant and Antimicrobial Properties of Different Types of Tissue of Cedrus brevifolia Henry Extracts.

This study aimed to determine the chemical composition of different types of tissue of Cedrus brevifolia Henry (Pinaceae) methanolic extracts, namely needles, twigs, branches, and bark. Cedrus brevifolia is a narrow endemic coniferous tree species of Cyprus, growing in a sole population in the mountainous area of Paphos Forest. Chemical analysis of the extracts was performed using liquid chromatography combined with time-of-flight high-resolution mass spectrometry (LC/Q-TOF/HRMS). The majority of the 36 compounds tentatively identified belonged to the flavonoids family. The extract of needles was the richest extract in terms of secondary metabolites. The extracts were studied for their antioxidant activity using the DPPH free radical scavenging assay. Additionally, the antibacterial activity was evaluated by determining both the minimum inhibitory concentration and the minimum bactericidal concentration against Staphylococcus aureus and Escherichia coli. All extracts demonstrated antioxidant property, while bark gave the highest antioxidant capacity (IC50 value of 0.011 mg/mL) compared to the other tissues. Antibacterial activity was observed against both types of bacteria, with the extract of branches presenting the strongest activity against S. aureus (MIC, 0.097 mg/mL and MBC, 0.195 mg/mL). This is the first time that extracts of needles, twigs, branches, and bark of C. brevifolia are compared regarding their chemical composition as well as their antimicrobial and antioxidant properties.

Combination of a 15-SNP Polygenic Risk Score and Classical Risk Factors for the Prediction of Breast Cancer Risk in Cypriot Women.

The PRS combines multiplicatively the effects of common low-risk single nucleotide polymorphisms (SNPs) and has the potential to be used for the estimation of an individual's risk for a trait or disease. PRS has been successfully implemented for the prediction of breast cancer risk. The combination of PRS with classical breast cancer risk factors provides a more comprehensive risk estimation and could, thus, improve risk stratification and personalized preventative strategies. In this study, we assessed the predictive performance of the combined effect of PRS15 with classical breast-cancer risk factors in Cypriot women using 1109 cases and 1177 controls from the MASTOS study. The PRS15 was significantly associated with an increased breast cancer risk in Cypriot women OR (95% CI) 1.66 (1.25-2.19). The integrated risk model obtained an AUC (95% CI) 0.70 (0.67-0.72) and had the ability to stratify women according to their disease status at the extreme deciles. These results provide evidence that the combination of PRS with classical risk factors may be used in the future for the stratification of Cypriot women based on their disease risk, and support its potential clinical utility for targeted preventative actions and population screening.

Authentication of the Botanical and Geographical Origin and Detection of Adulteration of Olive Oil Using Gas Chromatography, Infrared and Raman Spectroscopy Techniques: A Review.

Olive oil is among the most popular supplements of the Mediterranean diet due to its high nutritional value. However, at the same time, because of economical purposes, it is also one of the products most subjected to adulteration. As a result, authenticity is an important issue of concern among authorities. Many analytical techniques, able to detect adulteration of olive oil, to identify its geographical and botanical origin and consequently guarantee its quality and authenticity, have been developed. This review paper discusses the use of infrared and Raman spectroscopy as candidate tools to examine the authenticity of olive oils. It also considers the volatile fraction as a marker to distinguish between different varieties and adulterated olive oils, using SPME combined with gas chromatography technique.

Nutraceuticals-based therapeutic approach: recent advances to combat pathogenesis of Alzheimer's disease.

Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative disease accompanying memory deficits. The available pharmaceutical care has some limitations mostly entailing side effects, shelf-life, and patient's compliance. The momentous implications of nutraceuticals in AD have attracted scientists. Several preclinical studies for the investigation of nutraceuticals have been conducted.Areas covered: This review focuses on the potential use of a nutraceuticals-based therapeutic approach to treat and prevent AD. Increasing knowledge of AD pathogenesis has led to the discovery of new therapeutic targets including pathophysiological mechanisms and various cascades. Hence, the present contribution will attend to the most popular and effective nutraceuticals with proposed brief mechanisms entailing antioxidant, anti-inflammatory, autophagy regulation, mitochondrial homeostasis, and more. Therefore, even though the effectiveness of nutraceuticals cannot be dismissed, it is essential to do further high-quality randomized clinical trials.Expert opinion: According to the potential of nutraceuticals to combat AD as multi-target directed drugs, there is critical importance to assess them as feasible lead compounds for drug discovery and development. To the best of the authors' knowledge, modification of blood-brain barrier permeability, bioavailability, and features of randomized clinical trials should be considered in prospective studies.

Tantalizing role of p53 molecular pathways and its coherent medications in neurodegenerative diseases.

Neurodegenerative diseases are incongruous, commonly age-related disorders characterized by progressive neuronal loss, comprising the most prevalent being Alzheimer's disease, Parkinson's disease, and Huntington's disease. Perilous health states are anticipated following the neurodegeneration. Their etiology remains largely ambiguous, while various mechanisms are ascribed to their pathogenesis. A recommended conception is regarding the role of p53, as a transcription factor regulating numerous cellular pathways comprising apoptosis. Neuronal fates are a feasible occurrence that contributes to all neurodegenerative diseases. In this work, we review the research investigated the potential role of p53 in the pathogenesis of these diseases. We put special emphasis on intricate We not only describe aberrant changes in p53 level/activity observed in CNS regions affected by particular diseases but, most importantly, put special attention to the complicated reciprocal tuning connections prevailing between p53 and molecules considered in pathological hallmarks of these disorders. Natural and synthetic medications regulating p53 expression are regarded as well.

Discrimination of botanical origin of olive oil from selected Greek cultivars by SPME-GC-MS and ATR-FTIR spectroscopy combined with chemometrics.

BACKGROUND: Consumers today wish to know the botanical origin of the olive oil they purchase. The objective of the present study was the development of robust chemometric models based on gas chromatography-mass spectrometry (GC-MS) and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) for the purpose of botanical differentiation of three commercial Greek olive oil cultivars. RESULTS: Using the solid-phase microextraction technique (SPME), volatile compounds (VC) were obtained and analyzed by GC-MS. Five hydrocarbons and one ester were selected by the forward stepwise algorithm, which best discriminated the olive oil samples. From ATR-FTIR analysis, the spectral regions chosen from the forward stepwise algorithm were associated with CO stretching vibration of the esters of triglycerides and the CH bending vibrations of the CH2 aliphatic group and double bonds. Application of the supervised methods of linear and quadratic discriminant cross-validation analysis, based on VC data, provided a correct classification score of 97.4% and 100.0%, respectively. Corresponding statistical analyses were used in the mid-infrared spectra, by which 96.1% of samples were discriminated correctly. CONCLUSION: ATR-FTIR and SPME-GC-MS techniques in conjunction with the appropriate feature selection algorithm and classification methods proved to be powerful tools for the authentication of Greek olive oil. The proposed methodology could be used in an industrial setting for determination of the botanical origin of Greek olive oil. © 2020 Society of Chemical Industry.

Crocins from Crocus sativus L. in the Management of Hyperglycemia. In Vivo Evidence from Zebrafish.

Diabetes mellitus is a disease characterized by persistent high blood glucose levels and accompanied by impaired metabolic pathways. In this study, we used zebrafish to investigate the effect of crocins isolated from Crocus sativus L., on the control of glucose levels and pancreatic ß-cells. Embryos were exposed to an aqueous solution of crocins and whole embryo glucose levels were measured at 48 h post-treatment. We showed that the application of crocins reduces zebrafish embryo glucose levels and enhances insulin expression. We also examined whether crocins are implicated in the metabolic pathway of gluconeogenesis. We showed that following a single application of crocins and glucose level reduction, the expression of phosphoenolpyruvate carboxykinase1 (pck1), a key gene involved in glucose metabolism, is increased. We propose a putative role for the crocins in glucose metabolism and insulin management.

NGS Panel Testing of Triple-Negative Breast Cancer Patients in Cyprus: A Study of BRCA-Negative Cases.

In Cyprus, approximately 9% of triple-negative (estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor receptor 2-negative) breast cancer (TNBC) patients are positive for germline pathogenic variants (PVs) in BRCA1/2. However, the contribution of other genes has not yet been determined. To this end, we aimed to investigate the prevalence of germline PVs in BRCA1/2-negative TNBC patients in Cyprus, unselected for family history of cancer or age of diagnosis. A comprehensive 94-cancer-gene panel was implemented for 163 germline DNA samples, extracted from the peripheral blood of TNBC patients. Identified variants of uncertain clinical significance were evaluated, using extensive in silico investigation. Eight PVs (4.9%) were identified in two high-penetrance TNBC susceptibility genes. Of these, seven occurred in PALB2 (87.5%) and one occurred in TP53 (12.5%). Interestingly, 50% of the patients carrying PVs were diagnosed over the age of 60 years. The frequency of non-BRCA PVs (4.9%) and especially PALB2 PVs (4.3%) in TNBC patients in Cyprus appears to be higher compared to other populations. Based on these results, we believe that PALB2 and TP53 along with BRCA1/2 genetic testing could be beneficial for a large proportion of TNBC patients in Cyprus, irrespective of their age of diagnosis.

Real-World Setting Cost-Effectiveness Analysis Comparing Three Therapeutic Schemes of One-Year Adjuvant Trastuzumab in HER2-Positive Early Breast Cancer from the Cyprus NHS Payer Perspective.

INTRODUCTION: This study is one of the first real-world cost-effectiveness analyses of one-year adjuvant trastuzumab used in HER2-positive early female breast cancer in comparison to chemotherapy alone. It is just the second one in Europe, the first one in Cyprus, and the fourth one worldwide ever carried out using real-world data. METHODS: Using a Markov model (four health states), a cost-effectiveness analysis was carried out both over 20 years and for a lifetime horizon. The sampling method used in this study was the randomized sampling of 900 women. RESULTS: The findings for the 20-year horizon showed that all trastuzumab arms were more cost-effective, with a willingness-to-pay threshold of only €60,000 per quality-adjusted life year (QALY) [incremental cost-effectiveness ratios (ICER): €40,436.10/QALY]. For the lifetime horizon, with thresholds of €20,000, €40,000, and €60,000/QALY, all trastuzumab arms were found to be more cost-effective (ICER: €17,753.85/QALY). Moreover, for the 20-year and the lifetime horizons, with thresholds of €20,000/QALY, €40,000/QALY, and €60,000/QALY, the most cost-effective of the three subgroups (anthracyclines and then trastuzumab, no anthracyclines and then trastuzumab, and anthracyclines, taxanes, and trastuzumab) was that of anthracyclines and then trastuzumab (ICER: €18,301.55/QALY and €8954.97/QALY, respectively). CONCLUSIONS: The study revealed that adjuvant trastuzumab for one year in female HER2-positive early breast cancer can be considered cost-effective.

Characterization of the chemical composition of Drimia numidica plant parts using high-resolution mass spectrometry: study of their total phenolic content and antioxidant activity.

Drimia species have been used since ancient times for their medicinal properties. Their bulbs are considered as the main source of secondary metabolites with biological activity but the chemical composition of the other plant parts has not yet been considered. The aim of this study is to contribute to the existing knowledge with new data on the total phenolic content, the antioxidant activity and the chemical profile of different parts of Drimia numidica. The total phenolic content was estimated by the Folin-Ciocalteu assay and the antioxidant activity with DPPH· and ABTS·+ reagents. The separation and the identification of the compounds were performed with liquid chromatography combined with time-of-flight high-resolution mass spectrometry (LC/Q-TOF/HRMS). The extract of leaves presented the highest phenolic content while the highest antioxidant activity was presented by the extract of flowers. Results of the chemical analysis verify the presence of bufadienolides and phenolic compounds. Graphical abstract.

Antioxidant Properties of Crocus Sativus L. and Its Constituents and Relevance to Neurodegenerative Diseases; Focus on Alzheimer's and Parkinson's Disease.

BACKGROUND: Reactive oxygen species and reactive nitrogen species, which are collectively called reactive oxygen-nitrogen species, are the inevitable by-products of cellular metabolic redox reactions, such as oxidative phosphorylation in the mitochondrial respiratory chain, phagocytosis, reactions of biotransformation of exogenous and endogenous substrata in endoplasmic reticulum, eicosanoid synthesis, and redox reactions in the presence of metal with variable valence. Among medicinal plants, there is growing interest in Crocus Sativus L. It is a perennial, stemless herb, belonging to Iridaceae family, cultivated in various countries such as Greece, Italy, Spain, Israel, Morocco, Turkey, Iran, India, China, Egypt and Mexico. OBJECTIVE: The present study aims to address the protective role of Crocus Sativus L. in neurodegeneration with an emphasis in Parkinson's and Alzheimer's disease. MATERIALS AND METHODS: An electronic literature search was conducted by two of the authors from 1993 to August 2017. Original articles and systematic reviews (with or without meta-analysis), as well as case reports were selected. Titles and abstracts of papers were screened by a third reviewer to determine whether they met the eligibility criteria, and full texts of the selected articles were retrieved. RESULTS: Hence, the authors focused on the literature concerning the role of Crocus Sativus L. on its anti-oxidant and neuroprotective properties. CONCLUSION: Literature findings represented in current review herald promising results for using Crocus Sativus L. and/or its active constituents as antioxidants, anti-inflammatory, and neuroprotective agents.

Determination of acrylamide in food using a UPLC-MS/MS method: results of the official control and dietary exposure assessment in Cyprus.

The determination of acrylamide in potato products, bakery products and coffee, and the human dietary exposure is reported. The method reported is based on a single extraction step with water, followed by the clean-up of the extract using solid phase extraction columns and finally, the determination of acrylamide using UPLC-MS/MS. The MS/MS detection was carried out using an ESI interface in positive ion mode. Internal calibration was used for the quantification of acrylamide, because of the suppression/enhancement matrix effects due to the complex nature of the samples. The method performance characteristics were determined after spiking blank samples. The mean recoveries in spiked coffee samples, potato chips, breakfast cereals and crispbread ranged from 93% to 99%, with RSDs lower than 5% for both repeatability and reproducibility conditions. The estimated limits of detection and quantification of the method were 10 and 32 µg kg-1, respectively. The method was used for monitoring acrylamide in 406 samples. Acrylamide amounts ranged from <32 to 2450 µg kg-1. A total of 360 samples (89%) were contaminated with acrylamide, but only 14% of the samples exceeded the benchmark levels of the EU legislation. Foods with the highest mean acrylamide amounts were potato crisps (642 µg kg-1), French fries (383 µg kg-1) and biscuits (353 µg kg-1). The mean and 95th percentile acrylamide exposures of adolescents in Cyprus were 0.8 and 1.8 µg kg-1 body weight per day, respectively. The estimated levels of dietary exposure to acrylamide are not of concern with respect to neurotoxicity. However, the margins of exposure (MOEs) indicate a concern for carcinogenicity. Potato fried products (45%), fine bakery ware (21%) and potato chips (14%) contributed the most to overall acrylamide exposure.

Mediterranean diet-gene interactions: A targeted metabolomics study in Greek-Cypriot women.

SCOPE: A high adherence to the Mediterranean diet (MD) was previously associated with a decreased risk of breast cancer (BC) among Greek-Cypriot women. Additionally, particular polymorphisms were shown to modulate this MD-BC association. Herein, we aimed to investigate the effect of polymorphisms-MD interactions on the levels of specific metabolites that could be related to dietary adherence or enzymatic activity, which is itself modulated by polymorphisms. METHODS AND RESULTS: Greek-Cypriot women who were BC controls and had the lowest or the highest MD adherence (vegetables, fruit, legumes, fish) as assessed by principal component analysis (n = 564) were included. Participants were previously genotyped for nine polymorphisms of the one-carbon metabolism, oxidative stress, and xenobiotic metabolism. The serum levels of 14 metabolites that are key players in the aforementioned pathways were measured by UPLC-MS/MS. ANCOVA was used to assess polymorphism-MD interactions on metabolites' levels within a multivariate linear regression model. Statistically significant interactions between GSTM1 (where GST is glutathione S-transferase) deletion polymorphism and MD on flavin mononucleotide and on 5-methyltetrahydrofolate (5-MTHF) concentrations were observed. The MTHFR rs1801133 interacted significantly with MD on 5-MTHF concentration. CONCLUSION: Serum levels of flavin mononucleotide and 5-MTHF were shown to be influenced by interactions between GSTM1 deletion or MTHFR (rs1801133) polymorphisms and a dietary pattern, characteristic of MD.

Tumor-Suppressing Properties of Crocus sativus L.: Nature as an Anti-Cancer Agent.

Cancer is a growing problem because it is a chronic disease that affects, not only patient health, but also its daily living. Concurrent cancer therapies have ameliorated cancer prevalence, but the severity and frequency of toxicity and side effects during therapy have led the scientific community to rediscover the possible therapeutic effectiveness of herbs and spices. Crocus sativus L., commonly known as saffron, has been used in folk medicine for centuries. Today, data from numerous in vivo and in vitro studies support its anti-cancer activity, making it a promising anti-cancer agent for study. In the present review, we focus on the anti-cancer activity of C. sativus and its derivates. Medications that are currently used as chemotherapeutic or anti-cancer agents are associated with side effects whether used at effective doses or at levels that exceed the therapeutic dose. Therefore, many cancer survivors suffer from serious and even life-threatening long- or short-term sequelae, so the development of alternative/coadjutant drugs is imperative.