Flavonoids are ubiquitous in nature. They are also in food, providing an essential link between diet and prevention of chronic diseases including cancer. Anticancer effects of these polyphenols ...depend on several factors: Their chemical structure and concentration, and also on the type of cancer. Malignant cells from different tissues reveal somewhat different sensitivity toward flavonoids and, therefore, the preferences of the most common dietary flavonoids to various human cancer types are analyzed in this review. While luteolin and kaempferol can be considered as promising candidate agents for treatment of gastric and ovarian cancers, respectively, apigenin, chrysin, and luteolin have good perspectives as potent antitumor agents for cervical cancer; cells from main sites of flavonoid metabolism (colon and liver) reveal rather large fluctuations in anticancer activity probably due to exposure to various metabolites with different activities. Anticancer effect of flavonoids toward blood cancer cells depend on their myeloid, lymphoid, or erythroid origin; cytotoxic effects of flavonoids on breast and prostate cancer cells are highly related to the expression of hormone receptors. Different flavonoids are often preferentially present in certain food items, and knowledge about the malignant tissue-specific anticancer effects of flavonoids could be purposely applied both in chemoprevention as well as in cancer treatment.
Over the past few decades, it has become clear that an excessive activity of matrix metalloproteinases (MMPs) can accelerate the progression and fatal outcomes of several serious age-related ...diseases, including atherosclerotic coronary heart disorders and various types of malignancies. These proteolytic enzymes mediate the degradation and remodeling of the extracellular matrix through cleaving its various components, thereby affecting many critical functions of surrounding cells and intercellular communication. Consequently, the low expression levels of MMPs can be important in the prevention and treatment of such chronic life-threatening pathologies, contributing to the better quality of life and longer life expectancy. In this review article, the pathogenic proteolytic roles of MMPs are examined in more detail, especially in the cases of heart attack and stroke as well as cancer invasion and metastasis, showing that these enzymes can be considered not only as diagnostic and prognostic biomarkers but also as important therapeutic targets in the fight against many age- and lifestyle-related serious disorders. The identification and development of suppressing agents with a selective activity towards specific MMPs have, however, still remained a complex and complicated challenge, in which natural plant-derived compounds are increasingly recognized as promising leads for the new-generation inhibitors.
Compared to humans, plants can synthesize an extremely diverse array of chemical compounds, including phenolic acids, flavonoids, stilbenes, lignans, terpenoids, alkaloids, and many other types of ...secondary metabolites that have been demonstrated to exert important bioactivities and impacts on the human health. As a result of extensive and sustained efforts, some phytochemicals like vincristine, vinblastine, and paclitaxel have already been approved as anticancer drugs today, while several others are under clinical trials. However, despite this remarkable success, studies on anticancer action of plant-derived products have been and paradoxically are still in some places, mixed up with alternative approaches and thereby considered non-credible, especially in regions where the role of traditional medicine has not been historically so prevalent as in several Asian countries. As a result, only about 10% of higher plants have been explored regarding the potential therapeutic effects of their constituents. Moreover, as one function of secondary metabolites includes the protection of plants against diverse environmental stresses, the content and composition of these phytochemicals might importantly vary between different regional habitats. Therefore, the stereotyped attitudes to plant products as something related to alternative medicine must be changed to identify new lead molecules for novel anticancer drugs. It is possible that plants still harbor an important spectrum of pharmaceutically interesting, but still unidentified, chemical compounds.
Many of nowadays diseases are due to the oxidative stress resulting from imbalance between formation and neutralization of free radicals. Intake of dietary antioxidants is therefore crucial to ...maintain good health. As the safety of synthetic antioxidants has raised several questions the search for natural efficient antioxidants from chemicals produced by plants has gained increased popularity in recent years. Quercetin is an abundant dietary flavonoid with well-known radical scavenging properties being often used as a reference compound in many antioxidant tests. Its reaction with 1,1- diphenyl-2-picrylhydrazyl (artificial DPPH radical) is rapid and stoichiometric; however the published inhibitory constants vary in a very wide range, from 95 nM to 226 µM. The analysis indicates the dependence of antiradical capacity of quercetin on the composition of solvent systems where the reactions are performed and also on the surrounding temperature showing somewhat higher scavenging ability at body temperature compared to room conditions. At the same time, this activity is generally independent on the initial DPPH concentration. These data highlight the importance to consider the reaction environment and conditions when predicting the redox behavior of quercetin in a certain cellular context. Moreover, due to the changes in cellular environment accompanying with different pathogeneses the redox action of polyphenols can essentially vary leading even to the situations where the well-known antioxidant quercetin may reveal prooxidant properties.
Cervical cancer is the most common gynecologic malignancy worldwide and development of new therapeutic strategies and anticancer agents is an urgent priority. Plants have remained an important source ...in the search for novel cytotoxic compounds and several polyphenolic flavonoids possess antitumor properties. In this review article, data about potential anticarcinogenic activity of common natural flavonoids on various human cervical cancer cell lines are compiled and analyzed showing perspectives for the use of these secondary metabolites in the treatment of cervical carcinoma as well as in the development of novel chemotherapeutic drugs. Such anticancer effects of flavonoids seem to differentially depend on the cellular type and origin of cervical carcinoma creating possibilities for specific targeting in the future. Besides the cytotoxic activity per se, several flavonoids can also contribute to the increase in efficacy of conventional therapies rendering tumor cells more sensitive to standard chemotherapeutics and irradiation. Although the current knowledge is still rather scarce and further studies are certainly needed, it is clear that natural flavonoids may have a great potential to benefit cervical cancer patients.
In parallel with the continuous rise of cancer incidence, efficient treatment becomes an increasingly important public health concern. Radiotherapy has remained one of the most important anticancer ...approaches for clinical management of a variety of human tumors, as at least half of all oncological patients receive this therapy at some stages of their disease. With the hope to attain greater anticancer response, the interest in using natural plant-derived products as complementary treatments to conventional radiotherapy has substantially increased in the recent years. However, the interactions between phytochemicals and ionizing radiation are not always known and can be often unpredictable. Therefore, in this book, the current findings about the combined treatments of malignant cells with radiation and flavonoids, the largest group of human dietary plant polyphenols, are described. These data show that under carefully chosen dosage-schedule regimens, certain flavonoids or their natural mixtures can behave as potent radiosensitizers, augmenting radiotherapeutic efficacy in different preclinical cancer models. Such radiosensitizing action of flavonoids can be achieved through modulation of the redox status and suppression of several cellular survival pathways activated by radiotherapy, ultimately leading to the death of malignant cells. As flavonoids can concurrently protect normal healthy cells from irradiation-induced injury and thereby minimize toxic adverse reactions, use of these plant-derived agents as complementary approach to radiotherapy might open new avenues for enhancement of clinical outcome. Therefore, combining conventional anticancer modalities with conscious intake of flavonoid supplements as adjuvant agents might be an important future strategy to boost the therapeutic success in the treatment of various human malignancies.
Reactive oxygen species (ROS) play a pivotal role in biological processes and continuous ROS production in normal cells is controlled by the appropriate regulation between the silver lining of low ...and high ROS concentration mediated effects. Interestingly, ROS also dynamically influences the tumor microenvironment and is known to initiate cancer angiogenesis, metastasis, and survival at different concentrations. At moderate concentration, ROS activates the cancer cell survival signaling cascade involving mitogen-activated protein kinase/extracellular signal-regulated protein kinases 1/2 (MAPK/ERK1/2), p38, c-Jun N-terminal kinase (JNK), and phosphoinositide-3-kinase/ protein kinase B (PI3K/Akt), which in turn activate the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), matrix metalloproteinases (MMPs), and vascular endothelial growth factor (VEGF). At high concentrations, ROS can cause cancer cell apoptosis. Hence, it critically depends upon the ROS levels, to either augment tumorigenesis or lead to apoptosis. The major issue is targeting the dual actions of ROS effectively with respect to the concentration bias, which needs to be monitored carefully to impede tumor angiogenesis and metastasis for ROS to serve as potential therapeutic targets exogenously/endogenously. Overall, additional research is required to comprehend the potential of ROS as an effective anti-tumor modality and therapeutic target for treating malignancies.
Epigallocatechin gallate (EGCG), also known as epigallocatechin-3-gallate, is an ester of epigallocatechin and gallic acid. EGCG, abundantly found in tea, is a polyphenolic flavonoid that has the ...potential to affect human health and disease. EGCG interacts with various recognized cellular targets and inhibits cancer cell proliferation by inducing apoptosis and cell cycle arrest. In addition, scientific evidence has illustrated the promising role of EGCG in inhibiting tumor cell metastasis and angiogenesis. It has also been found that EGCG may reverse drug resistance of cancer cells and could be a promising candidate for synergism studies. The prospective importance of EGCG in cancer treatment is owed to its natural origin, safety, and low cost which presents it as an attractive target for further development of novel cancer therapeutics. A major challenge with EGCG is its low bioavailability which is being targeted for improvement by encapsulating EGCG in nano-sized vehicles for further delivery. However, there are major limitations of the studies on EGCG, including study design, experimental bias, and inconsistent results and reproducibility among different study cohorts. Additionally, it is important to identify specific EGCG pharmacological targets in the tumor-specific signaling pathways for development of novel combined therapeutic treatments with EGCG. The present review highlights the ongoing development to identify cellular and molecular targets of EGCG in cancer. Furthermore, the role of nanotechnology-mediated EGCG combinations and delivery systems will also be discussed.
Genistein is one among the several other known isoflavones that is found in different soybeans and soy products. The chemical name of genistein is 4',5,7-trihydroxyisoflavone. Genistein has drawn ...attention of scientific community because of its potential beneficial effects on human grave diseases, such as cancer. Mechanistic insight of genistein reveals its potential for apoptotic induction, cell cycle arrest, as well as antiangiogenic, antimetastatic, and anti-inflammatory effects.
The purpose of this review is to unravel and analyze various molecular mechanisms of genistein in diverse cancer models.
English language literature was searched using various databases, such as PubMed, ScienceDirect, EBOSCOhost, Scopus, Web of Science, and Cochrane Library. Key words used in various combinations included genistein, cancer, anticancer, molecular mechanisms prevention, treatment,
,
, and clinical studies.
Study selection was carried out strictly in accordance with the statement of Preferred Reporting Items for Systematic Reviews and Meta-analyses.
Four authors independently carried out the extraction of articles.
One hundred one papers were found suitable for use in this review.
This review covers various molecular interactions of genistein with various cellular targets in cancer models. It will help the scientific community understand genistein and cancer biology and will provoke them to design novel therapeutic strategies.
Hesperidin belongs to flavanones class of flavonoids and is known to possess broad-spectrum applicability to prevent dreadful diseases such as cardiovascular disease, neurodegeneration, and cancer. ...The reported anticancer effects of hesperidin have been found to be associated with its anti-oxidant and anti-inflammatory activities. Hesperidin interacts with numerous recognized cellular targets and inhibits cancer cell proliferation by inducing apoptosis and cell cycle arrest. In addition, evidence has suggested its promising role in inhibiting tumor cell metastasis, angiogenesis, and chemoresistance. The present mini-review highlights the ongoing development to identify hesperidin targets in cancer. Furthermore, the potential of nano technology-based hesperidin combinations and delivery systems will also be discussed. Overall, this review highlights all the possible molecular targets affected by hesperidin in tumor cells on a single platform.
Impact statement
Experimental findings from numerous studies have demonstrated the anticancer effects of hesperidin (Hesp) to be associated with anti-oxidant and anti-inflammatory activities along with its potential role in inhibiting the tumor cell metastasis and angiogenesis. Additionally, Hesp can also reverse drug resistance of cancer cells, which make it a promising candidate to be used in combination with existing anti-cancer drugs. This review will be helpful for upcoming researchers and scientific community to find out complete capsular package about cancer drug targets of Hesp and its role in modulating various important hallmarks of cancer.
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