Flavonoid-Based Nanomedicines to Target Tumor Microenvironment
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Abstract : Cancer cells arise and grow in tumor microenvironment which consists of stromal cells and extracellular matrix. The dynamic interaction between cancer cells and different components of the tumor microenvironment is a critical step in cancer development and progression. Several therapeutic strategies were explored as promising approaches to target tumor microenvironment. Flavonoids have gained increasing importance in cancer therapy due to their high bioavailability, low toxicity, and affordability. Many flavonoids showed potent activities as potential cytotoxic agents and multiple nano- formulations were tested to enhance the therapeutic effect of flavonoids. In this review, a comprehensive analysis of flavonoid-based nanomedicine was provided with special emphasis on tumor microenvironment components as therapeutic targets. Studies discussed in this review provide a solid ground for researchers and physicians to consider flavonoid based nano- formulations as possible adjuvant therapies with conventional anticancer agents.
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Combination Anticancer Therapies Using Selected Phytochemicals
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Abstract : Cancer is still one of the most widespread diseases globally, it is considered a vital health challenge worldwide and one of the main barriers to long life expectancy. Due to the potential toxicity and lack of selectivity of conventional chemotherapeutic agents, discovering alternative treatments is a top priority. Plant-derived natural products have high potential in cancer treatment due to their multiple mechanisms of action, diversity in structure, availability in nature, and relatively low toxicity. In this review, the anticancer mechanisms of the most common phytochemicals were analyzed. Furthermore, a detailed discussion of the anticancer effect of combinations consisting of natural product or natural products with chemotherapeutic drugs was provided. This review should provide a strong platform for researchers and clinicians to improve basic and clinical research in the development of alternative anticancer medicines.
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Chemoprevention effect of the Mediterranean diet on colorectal cancer: Current studies and future prospects
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Abstract : 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.
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Plants as a Source of Anticancer Agents: From Bench to Bedside
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Abstract : Cancer is the second leading cause of death after cardiovascular diseases. Conventional anticancer therapies are associated with lack of selectivity and serious side effects. Cancer hallmarks are biological capabilities acquired by cancer cells during neoplastic transformation. Targeting multiple cancer hallmarks is a promising strategy to treat cancer. The diversity in chemical structure and the relatively low toxicity make plant-derived natural products a promising source for the development of new and more effective anticancer therapies that have the capacity to target multiple hallmarks in cancer. In this review, we discussed the anticancer activities of ten natural products extracted from plants. The majority of these products inhibit cancer by targeting multiple cancer hallmarks, and many of these chemicals have reached clinical applications. Studies discussed in this review provide a solid ground for researchers and physicians to design more effective combination anticancer therapies using plant-derived natural products.
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Anticancer Effect of Spices Used in Mediterranean Diet: Preventive and Therapeutic Potentialsbr/>
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Abstract : 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.
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Chemical Composition, Antioxidant, Antimicrobial, and Immunomodulatory Activity of Mandragora autumnalis Grown in Jordan
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Abstract : Background The activity of phytochemicals has a huge impact on pharmaceutical research and on the process of developing new drugs. Hence, numerous studies have been conducted to investigate the efficacy of different natural products and their potential to be used in different types of therapy. Objective This study was carried out to investigate the biological activity of M. autumnalis crude extract and fractions, and the assessment was included antimicrobial activity, radical scavenging potential, and their effect on the immune system. The work also emphasizes determining the chemical constituents and the main bioactive compounds in M. autumnalis leaves. Methods Ethanol crude extract was prepared by maceration method, followed by solvents fractionation using n-hexane, aqueous/methanol, and water. Phytochemical analysis of ethanol extract using LC-MS was conducted as well as total phenolic and flavonoids content. The immunomodulatory activity was also evaluated by measuring the effect of M. autumnalis on splenocytes proliferation in the presence and absence of mitogens. Nitro blue tetrazolium assay and neutral red method have been used to determine the effect of M. autumnalis on the phagocytic activity of macrophages and the function of pinocytosis, respectively. Antibacterial assay was applied using microtiter plate dilution method, and DPPH assay was used to determine the antioxidant activity. Results The phytochemical analysis has shown the presence of flavonoids, polyphenolic compounds, and other organic acids like quinic and chlorogenic acids. M. autumnalis aqueous fraction exhibited high antioxidant activity with IC₅₀ value of 23.67±0.3 μg/ml. Ethanol extract and n-hexane fraction inhibited the bacterial growth of P. auriginosa with MIC value of 25 mg/ml, while n-hexane fraction was more active against C. albicans with MIC value of 12.5 mg/ml. On the other hand, the immune assay revealed a slight modulation of the lymphocyte and macrophages activity compared to the control results. Conclusion The results suggested that M. autumnalis leaves are rich in polyphenolic compounds and its crude extract and fractions exhibited antimicrobial and antioxidant potential. However, further research is needed to understand the effect of M. autumnalis on the immune parameters.
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Antioxidant and Antiproliferation Activities of Lemon Verbena (Aloysia citrodora): An In Vitro and In Vivo Study"
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Abstract : Aloysia citrodora (Verbenaceae) is traditionally used to treat various diseases, including bronchitis, insomnia, anxiety, digestive, and heart problems. In this study, this plant’s antioxidant and anti-proliferation effects were evaluated. In addition to volatiles extraction, different solvent extracts were prepared. The GC-MS, LC-MS analysis and the Foline-Ciocalteu (F-C) method were used to investigate the phytochemical components of the plant. MTT assay was used to measure the antiproliferative ability for each extract. Antioxidant activity was determined using the 2,2-diphenylpicrylhydrazyl (DPPH) assay. In in vivo anti-proliferation experiments, Balb/C mice were inoculated with tumor cells and IP-injected with ethyl acetate extract of A. citrodora. After treatment, a significant reduction in tumor size (57.97%) and undetected tumors (44.44%) were obtained in treated mice, demonstrating the antiproliferative efficacy of the ethyl acetate extract. Besides, ethanol extract revealed the most potent radical scavenging effect. The findings of this study displayed that A. citrodora has promising cytotoxic and antioxidant activities. Still, further testing is required to investigate the extract’s chemical composition to understand its mechanisms of action.
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Effect of Chalcogen Bonding Interactions on Molecular Structures; Theoretical and Crystallographic Studies on Two Palladium (II) acetate Complexes
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Abstract : Two palladium complexes, [Pd(L1)(OAc))] (1) and [Pd(L2)(OAc))] (2), have been synthesized by reacting Pd(OAc)2 and the new thioetherazo (HL) ligands (HL = 2(RS)C6H4NH-N=C(COCH3)-SC6H5, R= C6H5 (HL1), CH3 (HL2)). The ligands...
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Anticancer activity of Mandragora autumnalis: an in vitro and in vivo study
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Abstract : Ethanol crude extract and four solvent fractions were extracted from M. autumnalis leave to evaluate their anticancer effect in both models: in vitro and in vivo. The in vitro assessments were conducted using the MTT method in five cancer cell lines and one normal cell line. Ethanol extract and n-hexane fraction showed antitumor activity against MCF-7 breast cancer cells with IC₅₀ values of 0.1 and 0.4 mg/ml, respectively, and low cytotoxicity against normal VERO cell line (IC₅₀ value > 4 mg/ml). Furthermore, expression levels of VEGF were tested in MCF-7 cells treated with M. autumnalis using Human VEGF Simple Step ELISA Kit. The results indicated downregulation of VEGF expression in the treated cells compared to the control group. Additionally, the LD₅₀ of M. autumnalis ethanol extract was calculated by applying an acute toxicity assay. Balb/C mice were inoculated with EMT6/p breast cancer cells and then treated with (137 mg/kg/day intraperitoneal injection) of ethanol extract for ten days. Interestingly, a significant (p < 0.001) reduction occurred in the tumor size of the treated group compared to the control. Treatment in vivo toxicity was evaluated by measuring liver and kidney parameters. The tumor-bearing mice treated with the M. autumnalis extract showed normal serum level of AST, ALT, and creatinine. The results indicate that M. autumnalis has antitumor properties in both models in vitro and in vivo. However, a further molecular investigation is required to understand the molecular bearings of M. autumnalis' activity.
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Targeting Drug Chemo-Resistance in Cancer Using Natural Products
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Abstract : Cancer is one of the leading causes of death globally. The development of drug resistance is the main contributor to cancer-related mortality. Cancer cells exploit multiple mechanisms to reduce the therapeutic effects of anticancer drugs, thereby causing chemotherapy failure. Natural products are accessible, inexpensive, and less toxic sources of chemotherapeutic agents. Additionally, they have multiple mechanisms of action to inhibit various targets involved in the development of drug resistance. In this review, we have summarized the basic research and clinical applications of natural products as possible inhibitors for drug resistance in cancer. The molecular targets and the mechanisms of action of each natural product are also explained. Diverse drug resistance biomarkers were sensitive to natural products. P-glycoprotein and breast cancer resistance protein can be targeted by a large number of natural products. On the other hand, protein kinase C and topoisomerases were less sensitive to most of the studied natural products. The studies discussed in this review will provide a solid ground for scientists to explore the possible use of natural products in combination anticancer therapies to overcome drug resistance by targeting multiple drug resistance mechanisms.
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Ketogenic Diet in Cancer Prevention and Therapy: Molecular Targets and Therapeutic Opportunities
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Abstract : Although cancer is still one of the most significant global challenges facing public health, the world still lacks complementary approaches that would significantly enhance the efficacy of standard anticancer therapies. One of the essential strategies during cancer treatment is following a healthy diet program. The ketogenic diet (KD) has recently emerged as a metabolic therapy in cancer treatment, targeting cancer cell metabolism rather than a conventional dietary approach. The ketogenic diet (KD), a high-fat and very-low-carbohydrate with adequate amounts of protein, has shown antitumor effects by reducing energy supplies to cells. This low energy supply inhibits tumor growth, explaining the ketogenic diet’s therapeutic mechanisms in cancer treatment. This review highlights the crucial mechanisms that explain the ketogenic diet’s potential antitumor effects, which probably produces an unfavorable metabolic environment for cancer cells and can be used as a promising adjuvant in cancer therapy. Studies discussed in this review provide a solid background for researchers and physicians to design new combination therapies based on KD and conventional therapies.
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Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities
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Abstract : Melatonin is a pleotropic molecule with numerous biological activities. Epidemiological and experimental studies have documented that melatonin could inhibit different types of cancer in vitro and in vivo. Results showed the involvement of melatonin in different anticancer mechanisms including apoptosis induction, cell proliferation inhibition, reduction in tumor growth and metastases, reduction in the side effects associated with chemotherapy and radiotherapy, decreasing drug resistance in cancer therapy, and augmentation of the therapeutic effects of conventional anticancer therapies. Clinical trials revealed that melatonin is an effective adjuvant drug to all conventional therapies. This review summarized melatonin biosynthesis, availability from natural sources, metabolism, bioavailability, anticancer mechanisms of melatonin, its use in clinical trials, and pharmaceutical formulation. Studies discussed in this review will provide a solid foundation for researchers and physicians to design and develop new therapies to treat and prevent cancer using melatonin.
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Diabetes and Cancer: Metabolic Association, Therapeutic Challenges, and the Role of Natural Products
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Abstract : Cancer is considered the second leading cause of death worldwide and in 2018 it was responsible for approximately 9.6 million deaths. Globally, about one in six deaths are caused by cancer. A strong correlation was found between diabetes mellitus and carcinogenesis with the most evident correlation was with type 2 diabetes mellitus (T2DM). Research has proven that elevated blood glucose levels take part in cell proliferation and cancer cell progression. However, limited studies were conducted to evaluate the efficiency of conventional therapies in diabetic cancer patients. In this review, the correlation between cancer and diabetes will be discussed and the mechanisms by which the two diseases interact with each other, as well as the therapeutics challenges in treating patients with diabetes and cancer with possible solutions to overcome these challenges. Natural products targeting both diseases were discussed with detailed mechanisms of action. This review will provide a solid base for researchers and physicians to test natural products as adjuvant alternative therapies to treat cancer in diabetic patients.
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Palladium (II) Complexes of Azoithiophenyl Tridentate SNS Donor System: Synthesis, Spectroscopic Properties, Electrochemistry, Structural Characterization, and Biological Activity
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Plant-Derived Natural Products in Cancer Research: Extraction, Mechanism of Action, and Drug Formulation
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The Impact of Herbal Infusion Consumption on Oxidative Stress and Cancer: The Good, the Bad, the Misunderstood
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Abstract : The release of reactive oxygen species (ROS) and oxidative stress is associated with the development of many ailments, including cardiovascular diseases, diabetes and cancer. The causal link between oxidative stress and cancer is well established and antioxidants are suggested as a protective mechanism against cancer development. Recently, an increase in the consumption of antioxidant supplements was observed globally. The main sources of these antioxidants include fruits, vegetables, and beverage. Herbal infusions are highly popular beverages consumed daily for different reasons. Studies showed the potent antioxidant effects of plants used in the preparation of some herbal infusions. Such herbal infusions represent an important source of antioxidants and can be used as a dietary protection against cancer. However, uncontrolled consumption of herbal infusions may cause toxicity and reduced antioxidant activity. In this review, eleven widely consumed herbal infusions were evaluated for their antioxidant capacities, anticancer potential and possible toxicity. These herbal infusions are highly popular and consumed as daily drinks in different countries. Studies discussed in this review will provide a solid ground for researchers to have better understanding of the use of herbal infusions to reduce oxidative stress and as protective supplements against cancer development.
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