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Cancer, a leading global cause of mortality, arises from intricate interactions between genetic and environmental factors, fueling uncontrolled cell growth. Amidst existing treatment limitations, vitamins have emerged as promising candidates for cancer prevention and treatment. This review focuses on Vitamins A, C, E, and D because of their protective activity against various types of cancer. They are essential as human metabolic coenzymes. Through a critical exploration of preclinical and clinical studies via PubMed and Google Scholar, the impact of these vitamins on cancer therapy was analyzed, unraveling their complicated mechanisms of action. Interestingly, vitamins impact immune function, antioxidant defense, inflammation, and epigenetic regulation, potentially enhancing outcomes by influencing cell behavior and countering stress and DNA damage. Encouraging clinical trial results have been observed; however, further well-controlled studies are imperative to validate their effectiveness, determine optimal dosages, and formulate comprehensive cancer prevention and treatment strategies. Personalized supplementation strategies, informed by medical expertise, are pivotal for optimal outcomes in both clinical and preclinical contexts. Nevertheless, conclusive evidence regarding the efficacy of vitamins in cancer prevention and treatment is still pending, urging further research and exploration in this compelling area of study.

Colorectal cancer (CRC) is the third most common cancer and the second most deadly cancer worldwide. Nevertheless, more than 70% of CRC cases are resulted from sporadic tumorigenesis and are not inherited. Since adenoma-carcinoma development is a slow process and may take up to 20 years, diet-based chemoprevention could be an effective approach in sporadic CRC. The Mediterranean diet is an example of a healthy diet pattern that consists of a combination of nutraceuticals that prevent several chronic diseases and cancer. Many epidemiological studies have shown the correlation between adherence to the Mediterranean diet and low incidence of CRC. The goal of this review is to shed the light on the anti-inflammatory and anti-colorectal cancer potentials of the natural bioactive compounds derived from the main foods in the Mediterranean diet.

Breast cancer is considered a universal public health dilemma in women. Due to the high toxicity and low selectivity of conventional anticancer therapies, there is a growing trend of using plant-derived natural products in cancer prevention and therapy. Ashwagandha (Withania somnifera, WS) has been used in the Mediterranean region and Ayurvedic medicine for millennia as a functional food and a medicinal plant with anticancer activity. Besides, intermittent fasting (IF) has been engaged recently in cancer treatment. Hence, the combination of WS and IF provides possible solutions to treat cancer and reduce chemoresistance when combined with chemotherapy. In this study, WS root (WSR), IF, and cisplatin were tested on cisplatin-sensitive (EMT6/P) and cisplatin-resistant (EMT6/CPR) mouse mammary cell lines. The phytochemical content of the WSR extract was analyzed using liquid chromatography–mass spectrometry (LC-MS) analysis. Antiproliferative and apoptotic effects were assessed for WSR extract, cisplatin, and their combination in vitro using [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] (MTT) and caspase-3 assays. An in vivo study was used to assess the effect of WSR extract, IF, cisplatin, and their combinations in mice inculcated with EMT6/P and EMT6/CPR cells. The safety profile was also investigated using liver enzymes and creatinine assays. In vitro, WSR extract and cisplatin had a synergistic effect in both cell lines. The same combination induced an apoptotic effect higher than the single treatment in both cell lines. In vivo, several combinations of WSR extract, IF, or cisplatin caused significant tumor size reduction and improved the cure rate in mice implanted with EMT6/P and EMT6/CPR cell lines. IF-treated groups showed a significant reduction in serum glucose and an elevation in β-hydroxybutyrate (BHB) levels. In the safety profile, WSR extract, IF, and their combinations were safe. Overall, the combination of WSR extract and IF provides a promising solution for breast cancer treatment besides cisplatin by reducing the proliferation of cancer cells through induction of apoptosis. Moreover, they minimize cisplatin toxicity to the liver and kidney.

BackgroundFrom the earliest times, manna has been widely used as a tasty local sweet or folk medicine. The type of manna being investigated in the present study is called Gaz-alafi, a mixture of insect and Quercus brantii leaves secretions from oak forests in the north of Iraq and west of Iran.MethodsAqueous and ethanol extracts were prepared as decoction. Various phytochemical tests were conducted to analyze manna composition, including total phenolic contents using the Folin-Ciocalteu method and LC-MS. Gallic acid and catechin were detected in both extracts, in addition to tiliroside presence in ethanol extract, which added more value to the phenolic content of ethanol extract. Cytotoxic activities of Gaz alafi were evaluated against breast cancer cell lines and compared to normal cell lines and doxorubicin using the MTT assay. Antimicrobial properties were assessed against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, and Candida albicans using the dilution method of the micro-titer plate. Serum levels of IFN-γ, interleukin-2 (IL-2), interleukin-4 (IL-4), and interleukin-10 (IL-10) were measured using ELISA. The effect of extracts on splenocyte proliferation was evaluated using the lymphocytes proliferation assay. Macrophage function was evaluated using the nitro blue tetrazolium assay, whereas pinocytosis was evaluated using the neutral red uptake assay. Ten days after tumor inoculation, changes in tumor size, survival rates, levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine were measured.ResultsThe growth of cancer cells was inhibited by Gaz alafi ethanol extract. An alteration in IFN- γ, IL-2, and IL-4 levels toward antiproliferation immune response were reported for both extracts. The aqueous extract efficiently stimulated lymphocyte proliferation, phagocytosis, and pinocytosis, followed by the ethanol extracts with moderate activity. After treating the mice with ethanol extracts, a significant reduction in tumor size and several undetected tumors were recorded.ConclusionsGaz alafi extracts (aqueous and ethanol) are promising sources for anticancer and immunostimulatory agents. Further studies are needed to fully identify the chemical composition of Gaz alafi extracts.

Cancer is one of the leading causes of death worldwide, with almost 10 million cancer-related deaths worldwide in 2020, so any investigation to prevent or cure this disease is very important. Spices have been studied widely in several countries to treat different diseases. However, studies that summarize the potential anticancer effect of spices used in Mediterranean diet are very limited. This review highlighted chemo-therapeutic and chemo-preventive effect of ginger, pepper, rosemary, turmeric, black cumin and clove. Moreover, the mechanisms of action for each one of them were figured out such as anti-angiogenesis, antioxidant, altering signaling pathways, induction of cell apoptosis, and cell cycle arrest, for several types of cancer. The most widely used spice in Mediterranean diet is black pepper (Piper nigrum L). Ginger and black cumin have the highest anticancer activity by targeting multiple cancer hallmarks. Apoptosis induction is the most common pathway activated by different spices in Mediterranean diet to inhibit cancer. Studies discussed in this review may help researchers to design and test new anticancer diets enriched with selected spices that have high activities.

The Mediterranean diet is regarded as one of the most healthful dietary patterns in the world, owing to a combination of foods high in antioxidants and anticancer constituents. Barley bran is one of the components of the Mediterranean diet. It has nutritional and beneficial effects in different pathological conditions. Many studies were achieved to assess the nutritious values of barley bran, but there is no research indicating immunomodulatory and anticancer activities of barley bran grown in Jordan. The present study aims to examine and assess the potential immunomodulatory and anti-tumor activities of ethanol, n-hexane, aqueous/methanol, and water extracts obtained from barley bran. The Maceration method was utilized to prepare ethanol, n-hexane, aqueous/methanol, and water extracts. Various phytochemical groups were determined by using qualitative phytochemical tests. The antiproliferative activity of extracts was determined against MCF-7, HCT-116, A549, and EMT6/p by the MTT assay. The Folin-Ciocalteu reagent was used to detect the total phenolic content in extracts. Furthermore, immunomodulatory activity was assessed by determining the effect of extracts on splenocytes proliferation in the presence and absence of mitogens. The nitro blue tetrazolium assay and the neutral red method were used to assess the effect of each extract on the phagocytic activity of macrophages and pinocytosis, respectively. For the in vivo part, three different concentrations (10, 20, and 30% w/v) of barley bran were used to test the prophylactic effect in four Balb/C mice groups inoculated with EMT6/p cell-line subcutaneously. Also, serum samples were collected to assess the effect on cytokines (IFN-gamma, IL-2, IL-4, and IL-10). Barley bran extracts inhibited cancer cell proliferation. According to immunoassays, n-hexane and aqueous/methanol extracts could significantly rise lymphocyte proliferation and pinocytosis activity of macrophages. The activity of phagocytosis was increased by n-hexane and ethanol extracts. For the in vivo part, the average tumor size and weight of mice given the 30% barley bran group was significantly reduced (p < 0.05) compared with the control group. During our study, higher levels of TH1 cytokines (IFN- γ, IL-2) and lower levels of TH2 cytokine (IL-4) and T regulatory cytokine (IL-10) were obtained due to consumption of barley bran in food. Barley bran can be used as a prophylactic agent because it has anti-cancer and immunomodulatory activities.

The Mediterranean diet includes the consumption of various fruits and vegetables. Lemon and ginger are highly popular in Mediterranean cuisine. The current study aims to evaluate both anticancer and immunomodulatory activities of lemon and ginger combination. The antiproliferative activities of the combination were tested against different cancer cell lines using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. The degree of apoptosis induction and vascular endothelial growth factor expression were detected using ELISA. Balb/C mice were inoculated with the EMT6/P breast cancer cells and received combination water extract orally for 14 days. The effect of the water extract on splenocytes proliferation was measured using the mitogen proliferation assay. Macrophage function was evaluated using the nitro blue tetrazolium assay and pinocytosis was assessed using the neutral red method. Gas chromatography coupled to the tandem mass spectrometry was used to determine the composition of the combination. The lemon and ginger combination showed significant apoptosis induction and angiogenesis suppression effects. Fifty percent of the mice taking this combination did not develop tumors with a percentage of tumor reduction of 32.8%. This combination showed a potent effect in stimulating pinocytosis. Alpha-pinene and α-terpineol were detected in high percentages in the combination water extract. The lemon and ginger combination represents promising options to develop anticancer infusions for augmenting conventional anticancer therapies. Further testing is required to understand the exact molecular mechanisms of this combination.

Desert truffles have high nutritional value and grow wild in the Mediterranean basin and Western Asia. Although, many studies were performed to evaluate truffles nutritious values and phytochemical composition, studies are limited to evaluate their anticancer and/ or immunomodulatory effects. Our study was conducted to evaluate the anticancer and immunomodulatory effects of Terfezia boudieri (desert truffle). Different solvent extracts were prepared from the truffle and MTT assay was used to measure their anticancer activity against cancer cell lines (T47D, MCF-7, MDA-MB231, HCT-116, and Hela). Total phenolic content in each extract was determined by using Folin-Ciocalteu reagent and qualitative phytochemical screening was performed using standard methods. The degree of apoptosis induction (using caspase 3 assay) and vascular endothelial growth factor expression were detected using standard kits. Also, ELISA was used to measure levels of IFN-γ, IL-2, IL-4, and IL-10 secreted by splenocytes after treatment with the extracts. The effect of the extracts on splenocytes proliferation was measured using MTT assay. Macrophage function was evaluated using nitro blue tetrazolium assay and pinocytosis function was evaluated using neutral red method. Terpenoids, phytosterols, and carbohydrates were present in all the solvent extracts, while tannins, alkaloids and flavonoids were detected only in aqueous/methanol and aqueous extracts. The highest total phenolic content was observed in aqueous and aqueous methanol extracts. The growth of cancer cell lines was inhibited by T. boudieri extracts in a dose dependent manner. N-hexane extract was the most potent against most cell lines. Aqueous/methanol extract showed high apoptosis induction and angiogenesis suppression effects. An increase in TH1 cytokines (IFN-γ, IL-2) level and a decrease in TH2 cytokine (IL-4) level were evident after lymphocytes stimulation by aqueous/methanol, n-hexane and ethyl acetate extracts of T. boudieri. Ethyl acetate extract of T. boudieri were the most potent extracts to stimulate lymphocytes proliferation while all other extracts showed moderate stimulation. Aqueous/methanol extract was the most active extract to stimulate phagocytosis. Ethyl acetate extract was the most active extract to stimulate pinocytosis. The use of T. boudieri provides variable health benefits. N-hexane, ethyl acetate, and aqueous/methanol extracts exhibited anticancer activities and are potent stimulators of innate and acquired immunity. Further testing is needed to identify the biologically active compounds and detect them quantitatively using GC-MS analysis.