Phytosterols and the Digestive System: A Review Study from Insights into Their Potential Health Benefits and Safety.

Phytosterols are a large group of substances belonging to sterols-compounds naturally occurring in the tissues of plants, animals, and humans. The most well-known animal sterol is cholesterol. Among phytosterols, the most significant compounds are ß-sitosterol, stigmasterol, and campesterol. At present, they are mainly employed in functional food products designed to counteract cardiovascular disorders by lowering levels of 'bad' cholesterol, which stands as their most extensively studied purpose. It is currently understood that phytosterols may also alleviate conditions associated with the gastrointestinal system. Their beneficial pharmacological properties in relation to gastrointestinal tract include anti-inflammatory and hepatoprotective activity. Also, the anti-cancer properties as well as the impact on the gut microbiome could be a very interesting area of research, which might potentially lead to the discovery of their new application. This article provides consolidated knowledge on a new potential use of phytosterols, namely the treatment or prevention of gastrointestinal diseases. The cited studies indicate high therapeutic efficacy in conditions such as peptic ulcer disease, IBD or liver failure caused by hepatotoxic xenobiotics, however, these are mainly in vitro or in vivo studies. Nevertheless, studies to date indicate their therapeutic potential as adjunctive treatments to conventional therapies, which often exhibit unsatisfactory efficacy or serious side effects. Unfortunately, at this point there is a lack of significant clinical study data to use phytosterols in clinical practice in this area.

2D and 3D anticancer properties of C2-functionalised glucosamine-Pt (IV) prodrugs based on cisplatin scaffold.

A series of C2-functionalied Pt (IV) glycoconjugates based on glucosamine have been synthesised, characterised and tested as anticancer agents on a series of different 2D and 3D cancer cell lines. The carbohydrate will act as a targeted delivery system to improve the selectivity, exploiting the Warburg Effect and the GLUTs receptors that are overexpressed in most of the cancer cells. The hydroxyl at C2 of the carbohydrates does not participate in hydrogen bonding with the GLUTs receptors, making C2 an attractive position for drug conjugation as seen in literature. In this study, we use the amino functionality at the C2 position in glucosamine and Copper-catalysed Azide-Alkyne Cycloaddition "click" (CuAAC) reaction to connect the prodrug Pt (IV) scaffold to the carbohydrate. We have investigated complexes with different linker lengths, as well as acetyl protected and free derivatives. To the best of our knowledge, this study represents the first series of Pt (IV) glucosamine-conjugates functionalised at C2.

Oridonin from Rabdosia rubescens: An emerging potential in cancer therapy - A comprehensive review.

Cancer incidences are rising each year. In 2020, approximately 20 million new cancer cases and 10 million cancer-related deaths were recorded. The World Health Organization (WHO) predicts that by 2024 the incidence of cancer will increase to 30.2 million individuals annually. Considering the invasive characteristics of its diagnostic procedures and therapeutic methods side effects, scientists are searching for different solutions, including using plant-derived bioactive compounds, that could reduce the probability of cancer occurrence and make its treatment more comfortable. In this regard, oridonin (ORI), an ent-kaurane diterpenoid, naturally found in the leaves of Rabdosia rubescens species, has been found to have antitumor, antiangiogenesis, antiasthmatic, antiinflammatory, and apoptosis induction properties. Extensive research has been performed on ORI to find various mechanisms involved in its anticancer activities. This review article provides an overview of ORI's effectiveness on murine and human cancer populations from 1976 to 2022 and provides insight into the future application of ORI in different cancer therapies.

Illuminating new possibilities: Effects of copper oxide nanoparticles on gastrointestinal adenocarcinoma cells in hypoxic condition.

Cancer remains a major global health concern, necessitating the development of novel therapeutic approaches. Hypoxia is a common characteristic of solid tumors that plays a critical role in tumor progression, making it a prime target for anticancer therapies. This study aimed to determine the effects of copper oxide nanoparticles (CuONPs) on human gastrointestinal cancer cells in hypoxic condition for the first time. Toxicity of CuONPs was evaluated on human colon and gastric adenocarcinoma cells and normal fibroblasts by alamarBlue assay. Real-time polymerase chain reaction (PCR) was performed to study the effects of CuONPs on genes involved in cell apoptosis. To elucidate the molecular mechanisms underlying the effects of CuONPs in hypoxic condition, molecular docking was conducted on HIF-1α. Results revealed dose- and cell-type-dependent toxic effects of CuONPs, as a more significant (p < 0.0001) decrease in viability of LoVo cells (23 %) was observed compared to MKN-45 and HDF cells. In addition, CuONPs significantly (p < 0.0001) reduced LoVo cell viability down to 30.2 % in hypoxic condition. Gene expression analysis revealed significant (p < 0.0001) overexpression of P53 and BAX but downregulation of BCL-2 and CCND1 after treatment with CuONPs. Molecular docking indicated the preferable binding of CuONPs to the HIF-1α PAS-B domain through interaction with 15 residues with -4.8 kcal/mol binding energy. Our findings open up new possibilities for modulating HIF-1 activity and inhibiting hypoxia-induced tumor progression.

Nutritional Sources and Anticancer Potential of Phenethyl Isothiocyanate: Molecular Mechanisms and Therapeutic Insights.

Phenethyl isothiocyanate (PEITC), a compound derived from cruciferous vegetables, has garnered attention for its anticancer properties. This review synthesizes existing research on PEITC, focusing on its mechanisms of action in combatting cancer. PEITC has been found to be effective against various cancer types, such as breast, prostate, lung, colon, and pancreatic cancers. Its anticancer activities are mediated through several mechanisms, including the induction of apoptosis (programmed cell death), inhibition of cell proliferation, suppression of angiogenesis (formation of new blood vessels that feed tumors), and reduction of metastasis (spread of cancer cells to new areas). PEITC targets crucial cellular signaling pathways involved in cancer progression, notably the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), Protein Kinase B (Akt), and Mitogen-Activated Protein Kinase (MAPK) pathways. These findings suggest PEITC's potential as a therapeutic agent against cancer. However, further research is necessary to determine the optimal dosage, understand its bioavailability, and assess potential side effects. This will be crucial for developing PEITC-based treatments that are both effective and safe for clinical use in cancer therapy.

Bee Venom: Composition and Anticancer Properties.

Among the various natural compounds used in alternative and Oriental medicine, toxins isolated from different organisms have had their application for many years, and Apis mellifera venom has been studied the most extensively. Numerous studies dealing with the positive assets of bee venom (BV) indicated its beneficial properties. The usage of bee products to prevent the occurrence of diseases and for their treatment is often referred to as apitherapy and is based mainly on the experience of the traditional system of medical practice in diverse ethnic communities. Today, a large number of studies are focused on the antitumor effects of BV, which are mainly attributed to its basic polypeptide melittin (MEL). Previous studies have indicated that BV and its major constituent MEL cause a strong toxic effect on different cancer cells, such as liver, lung, bladder, kidney, prostate, breast, and leukemia cells, while a less pronounced effect was observed in normal non-target cells. Their proposed mechanisms of action, such as the effect on proliferation and growth inhibition, cell cycle alterations, and induction of cell death through several cancer cell death mechanisms, are associated with the activation of phospholipase A2 (PLA2), caspases, and matrix metalloproteinases that destroy cancer cells. Numerous cellular effects of BV and MEL need to be elucidated on the molecular level, while the key issue has to do with the trigger of the apoptotic cascade. Apoptosis could be either a consequence of the plasmatic membrane fenestration or the result of the direct interaction of the BV components with pro-apoptotic and anti-apoptotic factors. The interaction of BV peptides and enzymes with the plasma membrane is a crucial step in the whole process. However, before its possible application as a remedy, it is crucial to identify the correct route of exposure and dosage of BV and MEL for potential therapeutic use as well as potential side effects on normal cells and tissues to avoid any possible adverse event.

Adzuki and Mung Bean Sprouts Enriched with Probiotic Lactiplantibacillus plantarum 299v Improve Body Mass Gain and Antioxidant Status and Reduce the Undesirable Enzymatic Activity of Microbiota in Healthy Rats.

Introducing and establishing new food requires a detailed evaluation of its safety, nutritional value and functionality, thus the control and probiotic-rich adzuki and mung bean sprouts were studied in an in vivo rats model. However, the total feed intake did not differ significantly between the groups, the highest body weight gain and body weight change were recorded in the control AIN diet. At the same time, the addition of legume sprouts caused a reduction of these parameters (up to 25% in the variant with probiotic-rich adzuki bean sprouts). There was no significant effect on serum morphology, except white blood cells (ca. 20% reduction in the control sprout-supplemented diets). Serum and liver antiradical properties were significantly elevated by consuming mung bean sprouts (no effect of the probiotics). The faecal lactic acid bacteria were already increased by the control sprouts (a 2.8- and 2.1-fold increase for adzuki and mung bean sprouts, respectively). The probiotic-rich sprouts further improved this parameter. The diets enriched with mung bean sprouts significantly decreased the urease (by ca. 65%) and ß-glucuronidase activities (by ca. 30%). All the tested diets caused also a significant reduction of faecal tryptophanase activity (the effect was intensified by Lactiplantibacillus plantarum 299v). The functional components did not affect negatively the nutritional parameters and blood morphological characteristics. They improved also the antioxidant potential and significantly decreased the activities of colon cancer-related enzymes (urease and tryptophanase). The results confirmed that these new probiotic carriers may be a valuable, safe and functional element of a healthy diet.

Recent Developments in Nanoparticle Formulations for Resveratrol Encapsulation as an Anticancer Agent.

Resveratrol is a polyphenolic compound that has gained considerable attention in the past decade due to its multifaceted therapeutic potential, including anti-inflammatory and anticancer properties. However, its anticancer efficacy is impeded by low water solubility, dose-limiting toxicity, low bioavailability, and rapid hepatic metabolism. To overcome these hurdles, various nanoparticles such as organic and inorganic nanoparticles, liposomes, polymeric nanoparticles, dendrimers, solid lipid nanoparticles, gold nanoparticles, zinc oxide nanoparticles, zeolitic imidazolate frameworks, carbon nanotubes, bioactive glass nanoparticles, and mesoporous nanoparticles were employed to deliver resveratrol, enhancing its water solubility, bioavailability, and efficacy against various types of cancer. Resveratrol-loaded nanoparticle or resveratrol-conjugated nanoparticle administration exhibits excellent anticancer potency compared to free resveratrol. This review highlights the latest developments in nanoparticle-based delivery systems for resveratrol, focusing on the potential to overcome limitations associated with the compound's bioavailability and therapeutic effectiveness.

Genomics-driven derivatization of the bioactive fungal sesterterpenoid variecolin: Creation of an unnatural analogue with improved anticancer properties.

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin (1) and variecolactone (2) was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues (5-7). Analysis of the compounds' anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities, 5 was associated with significantly reduced toxic side effects in cancer-bearing mice, indicating its potentially broader therapeutic window. Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

Regulation of gene expression by modulating microRNAs through Epigallocatechin-3-gallate in cancer.

Cancer is an intricate ailment that has a higher death rate globally and is characterized by aberrant cell proliferation and metastasis in nature. Since the beginning of healthcare, natural products, especially those derived from plants, have been utilized to support human health. Green tea contains an essential catechin called epigallocatechin gallate, which has anti-proliferative, anti-mutagenic, anti-inflammatory, and antioxidative properties. The anticancer properties of EGCG have been extensively studied using pre-clinical cell culture and animal model systems. Dysregulated miRNA may be a biomarker since it influences the different characteristics of cancer like upholding proliferative signaling, cell death, invasiveness, metastasis, and angiogenesis. EGCG either elevates or lowers the expression of dysregulated miRNAs in cancer. Nonetheless, due to its anticancer properties, greater attention has been paid towards the development of efficient strategies for utilizing EGCG in cancer chemotherapy. This review summarizes the modifying effect of EGCG on miRNAs in cancer after briefly discussing the anticancer mechanisms of EGCG and the function of miRNAs in cancer.

Ippia Alba Essential Oil: A Promising Complementary Therapy for Breast Cancer.

Breast cancer remains a pressing global health issue, spurring exploration into innovative therapies. This review focuses on Lippia alba (Mill.) essential oil's potential as a complementary breast cancer treatment. With growing interest in natural approaches, Lippia alba shows promise in breast cancer management. The review will explore Lippia alba's multifaceted role in treatment, highlighting its anticancer effects on breast cancer cells, potential synergy with conventional treatments, safety profiles, and existing clinical evidence. It will also address knowledge gaps, stressing the need for further research to unlock Lippia alba's full therapeutic potential in breast cancer therapy. In a field craving novel therapies, this review offers a timely analysis. Despite the lack of existing reviews on this topic, Lippia alba's significance cannot be understated. As research progresses, this article will be a valuable resource for researchers and healthcare practitioners seeking to augment breast cancer management through complementary therapies.

Genomics-driven derivatization of the bioactive fungal sesterterpenoid variecolin: Creation of an unnatural analogue with improved anticancer properties

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin ( 1) and variecolactone ( 2) was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues ( 5- 7). Analysis of the compounds' anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities, 5 was associated with significantly reduced toxic side effects in cancer-bearing mice, indicating its potentially broader therapeutic window. Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

Probiotic Potential, Antiproliferative, and Proapoptotic Activities of Lactobacillus fermentum Isolated from Breast Milk.

Background: Breast milk is always the best choice for infant's nutrition due to its useful compounds such as immune cells and molecules, oligosaccharides, as well as bacteria and their metabolites. We identified and characterized the isolated strain from human breast milk in this study. Materials and Methods: A total of 20 lactating mothers aged 25 to 34 years were enrolled in our study. We collected the breast milk samples in sterile microtubes. 100 µl of each sample was spread on de Man-Rogosa-Sharpe (MRS) agar plates and incubated aerobically at 37°C for 48 hr. After identifying the isolated strain, initial tests (hemolysis inactivity and L-arginine hydrolysis, catalase), the acid tolerance, bile tolerance, and antibiotics susceptibility of the isolated strain were estimated. Furthermore, the antiproliferative and proapoptotic activities of heat-killed cells) HKC) and cell-free supernatant (CFS) of the strain on the HT-29 cell line were evaluated using MTT assay and flow cytometry analysis, respectively. Results: The isolated strain was Gram-positive, bacilli in shape, catalase-negative, non-hemolytic, and negative for L-arginine hydrolysis. By 16S rRNA gene sequencing, the isolated strain was Lactobacillus fermentum. According to MTT assay and flow cytometry results, the HKC and CFS of the isolated strain reduced the viability of the HT-29 cells. The total apoptosis induced in HT-29 cells by HKC and CFS was 65.98% and 70.1%, respectively. Conclusion: Our findings suggest that this strain, despite the properties of probiotic bacteria, has potential antiproliferative and proapoptotic capabilities.

Cellular Mechanisms of Singlet Oxygen in Photodynamic Therapy.

In this review, we delve into the realm of photodynamic therapy (PDT), an established method for combating cancer. The foundation of PDT lies in the activation of a photosensitizing agent using specific wavelengths of light, resulting in the generation of reactive oxygen species (ROS), notably singlet oxygen (1O2). We explore PDT's intricacies, emphasizing its precise targeting of cancer cells while sparing healthy tissue. We examine the pivotal role of singlet oxygen in initiating apoptosis and other cell death pathways, highlighting its potential for minimally invasive cancer treatment. Additionally, we delve into the complex interplay of cellular components, including catalase and NOX1, in defending cancer cells against PDT-induced oxidative and nitrative stress. We unveil an intriguing auto-amplifying mechanism involving secondary singlet oxygen production and catalase inactivation, offering promising avenues for enhancing PDT's effectiveness. In conclusion, our review unravels PDT's inner workings and underscores the importance of selective illumination and photosensitizer properties for achieving precision in cancer therapy. The exploration of cellular responses and interactions reveals opportunities for refining and optimizing PDT, which holds significant potential in the ongoing fight against cancer.

Experimental and theoretical investigations of Erbium complex: DNA/BSA interaction, anticancer and antibacterial studies.

To assess the biological potential of an Er complex that contains a 2,2'-bipyridine ligand, various techniques such as multispectral and molecular modeling procedures were utilized to examine its DNA-binding ability, BSA binding affinity, antimicrobial effects, and anticancer properties. By analyzing fluorescent information and employing the vant' Hoff equation, important parameters such as the innate docking coefficient (Kb), Stern-Volmer coefficient (KSV), and thermodynamic properties including modifications in liberated energy (ΔG°), enthalpy (∆H°), and entropy (∆S°) were determined. The trial findings suggest that the compound can bind to DNA, primarily through groove binding. Additionally, the engagement between the Er compound and the protein BSA was examined using emission spectroscopy technique, revealing a powerful binding affinity between the compound and BSA. The Er complex binds to BSA primarily via hydrogen links and van der Waals forces, as indicated by the adverse values of ΔH° and ∆S°. Through a static quenching process, the complex significantly reduces the intrinsic fluorescence of BSA. Molecular binding calculations and rivalrous binding trials confirm that this compound dock to hydrophobic remains found in site III of BSA. Additionally, the Er complex demonstrates promising results in terms of its anticancer and antimicrobial activities based on screening tests.

Enhancing Healthcare Outcomes and Modulating Apoptosis- and Antioxidant-Related Genes through the Nano-Phytosomal Delivery of Phenolics Extracted from Allium ampeloprasum.

The application of nano drug delivery systems, particularly those utilizing natural bioactive compounds with anticancer properties, has gained significant attention. In this study, a novel nano-phytosome-loaded phenolic rich fraction (PRF) derived from Allium ampeloprasum L. was developed. The antitumor activity of the formulation was evaluated in BALB/c mice with TUBO colon carcinoma. The PRF-loaded nano-phytosome (PRF-NPs) exhibited a sphere-shaped structure (226 nm) and contained a diverse range of phenolic compounds. Animal trials conducted on TUBO tumor-bearing mice demonstrated that treatment with PRF-NPs at a dosage of 50 mg TPC/Kg/BW resulted in significant improvements in body weight and food intake, while reducing liver enzymes and lipid peroxidation. The expression of apoptosis-related genes, such as Bax and caspase-3, was upregulated, whereas Bcl2 was significantly downregulated (p < 0.05). Furthermore, the expression of GPx and SOD genes in the liver was notably increased compared to the control group. The findings suggest that the phytosomal encapsulation of the phenolic rich fraction derived from Allium ampeloprasum L. can enhance the bioavailability of natural phytochemicals and improve their antitumor properties. The development of PRF-NPs as a nano drug delivery system holds promise for effective breast cancer treatment.

5-Amino-8-hydroxyquinoline-containing Electrospun Materials Based on Poly(vinyl alcohol) and Carboxymethyl Cellulose and Their Cu2+ and Fe3+ Complexes with Diverse Biological Properties: Antibacterial, Antifungal and Anticancer.

Novel fibrous materials with diverse biological properties containing a model drug of the 8-hydroxyquinoline group-5-amino-8-hydroxyquinoline (5A8Q)-were fabricated using a one-pot method by electrospinning poly(vinyl alcohol) (PVA)/carboxymethyl cellulose (CMC)/5A8Q solutions. Experiments were performed to prepare Cu2+ (Fe3+) complexes of the crosslinked PVA/CMC/5A8Q materials. The formation of complexes was proven by using scanning electron microscopy (SEM), attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy, energy-dispersive X-ray spectroscopy (EDX) and X-ray photoelectron spectroscopy (XPS). The release of 5A8Q and 5A8Q.Cu2+ (Fe3+) was studied and their in vitro release profiles were mostly impacted by the hydrophilic/hydrophobic properties of the materials. The performed microbiological assays revealed that fibrous materials containing 5A8Q and their complexes exhibited good antibacterial and antifungal efficacy. Their activity was stronger against bacteria S. aureus than against bacteria E. coli and fungi C. albicans. Cell viability tests using MTT showed that the presence of 5A8Q and its complexes in the fibrous materials resulted in a significant decrease in the HeLa and MCF-7 cancer cell viability for the various times of cell incubation. Moreover, the observed cytotoxicity of the mats against cancer cells was greater than that against non-cancer HaCaT keratinocytes. All these properties make the novel materials potential candidates for the design of wound healing materials and as drug delivery systems for local therapy of cervical and breast cancer.

Targeting autophagy with tamoxifen in breast cancer: From molecular mechanisms to targeted therapy.

BACKGROUND: Tamoxifen (TAM) is often recommended as a first-line treatment for estrogen receptor-positive breast cancer (BC). However, TAM resistance continues to be a medical challenge for BC with hormone receptor positivity. The function of macro-autophagy and autophagy has recently been identified to be altered in BC, which suggests a potential mechanism for TAM resistance. Autophagy is a cellular stress-induced response to preserve cellular homeostasis. Also, therapy-induced autophagy, which is typically cytoprotective and activated in tumor cells, could sometimes be non-protective, cytostatic, or cytotoxic depending on how it is regulated. OBJECTIVE: This review explored the literature on the connections between hormonal therapies and autophagy. We investigated how autophagy could develop drug resistance in BC cells. METHODS: Scopus, Science Direct, PubMed, and Google Scholar were used to search articles for this study. RESULTS: The results demonstrated that protein kinases such as pAMPK, BAX, and p-p70S6K could be a sign of autophagy in developing TAM resistance. According to the study's findings, autophagy plays an important role in BC patients' TAM resistance. CONCLUSION: Therefore, by overcoming endocrine resistance in estrogen receptor-positive breast tumors, autophagy inhibition may improve the therapeutic efficacy of TAM.

An evaluation of antibacterial properties and cytotoxicity of UV-curable biocompatible films containing hydroxyethyl cellulose and silver nanoparticles.

The present study aimed to develop biocompatible film materials with antibacterial and anticancer properties that can be cured with UV rays depending on the thiol-en click reaction mechanism. The synthesized m-Ag NPs were added to formulations containing acrylate functionality HEC, pentaerythritol tetrarkis(3-mercaptopropionate), and photoinitiator at different rates (0, 20, 40, and 60 parts per hundred (phr)). The antibacterial activity of the films was evaluated against S. aureus, P. aeruginosa and E. coli by the disk diffusion test. The antibacterial effect of the films did not form an inhibition zone for the control formulation (Cm-Ag0 ) against bacteria whereas the antibacterial property increased as the Ag NPs content increased in formulations containing m-Ag NPs. The strongest resistance film against the three bacterial species was observed in the Cm-Ag60 formulation with 60 phr silver content, and the inhibition zones for S. aureus, P. aeruginosa, and E. coli were measured as 16.5 ± 0.7, 16.5 ± 2.1, and 16 ± 1.4, respectively. The cytotoxicity of the films against healthy cells and breast cancer cell (MCF-7) lines was investigated with MTT, and it was observed that all films did not cause any inhibition in the structure of the living cell but killed the cells at a high rate in the MCF-7 line. It was mainly observed that the Cm-Ag60 formulation showed 95.576 % cell inhibition against MCF-7. According to these results, it has been predicted that the prepared films will play a vital role in the next generation of cancer treatments.

A Systematic Ex-Vivo Study of the Anti-Proliferative/Cytotoxic Bioactivity of Major Olive Secoiridoids' Double Combinations and of Total Olive Oil Phenolic Extracts on Multiple Cell-Culture Based Cancer Models Highlights Synergistic Effects.

Several individual olive oil phenols (OOPs) and their secoiridoid derivatives have been shown to exert anti-proliferative and pro-apoptotic activity in treatments of human cancer cell lines originating from several tissues. This study evaluated the synergistic anti-proliferative/cytotoxic effects of five olive secoiridoid derivatives (oleocanthal, oleacein, oleuropein aglycone, ligstroside aglycone and oleomissional) in all possible double combinations and of total phenolic extracts (TPEs) on eleven human cancer cell lines representing eight cell-culture-based cancer models. Individual OOPs were used to treat cells for 72 h in half of their EC50 values for each cell line and their synergistic, additive or antagonistic interactions were evaluated by calculating the coefficient for drug interactions (CDI) for each double combination of OOPs. Olive oil TPEs of determined OOPs' content, originating from three different harvests of autochthonous olive cultivars in Greece, were evaluated as an attempt to investigate the efficacy of OOPs to reduce cancer cell numbers as part of olive oil consumption. Most combinations of OOPs showed strong synergistic effect (CDIs < 0.9) in their efficacy, whereas TPEs strongly impaired cancer cell viability, better than most individual OOPs tested herein, including the most resistant cancer cell lines evaluated.