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Impact of DNA methylation and histone-modifying enzymes on the regulation of genes commonly deregulated during carcinogenesis. Inhibition/ modulation of the activity or expression of DNMTs or histone-modifying proteins by chemopreventive agents can lead to reactivation of epigenetically silenced genes. See text for a detailed description of the indicated mechanisms and pathways and the influence of chemopreventive agents
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The term “epigenetics” refers to modifications in gene expression caused by heritable, but potentially reversible, changes in DNA methylation and chromatin structure. Epigenetic alterations have been identified as promising new targets for cancer prevention strategies as they occur early during carcinogenesis and represent potentially initiating ev...
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... chapter will focus on pathways which are relevant for chemopre- vention and are commonly deregulated by epigenetic mechanisms in cancer cells, including drug detoxification, cell cycle regulation, apoptosis induction, DNA repair, tumor-associated inflammation, cell signaling that promotes cell growth, and cell differentiation (overview in Fig. 4). It will present a summary of natural chemopreventive agents targeting these pathways by affecting DNA methylation and histone tail modifications. Their effect on miRNAs and subsequent gene expression will not be ...
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Colorectal cancer (CRC) is distinguished by epigenetic elements like DNA methylation, histone modification, histone acetylation and RNA remodeling which is related with genomic instability and tumor initiation. Correspondingly, as a main epigenetic regulation, DNA methylation has an impressive ability in order to be used in CRC targeted therapy. Me...
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... For example, "Curcumin" is a polyphenol extract from the rhizome of curcuma longa plant, and is demonstrated to possess anti-tumor activity against various cancers (Ma et al., 2014;Shah et al., 2015). Accordingly, its tumor limiting potential is traced back to its ability to modulate the expression of transcription factors, cytokines, cellular receptor, enzymes, kinases as well as growth factors (Gerhauser, 2013). In addition, it is also reported to sensitize cancer cells to chemotherapeutic treatments (Gerhauser, 2013;Shah et al., 2015). ...
... Accordingly, its tumor limiting potential is traced back to its ability to modulate the expression of transcription factors, cytokines, cellular receptor, enzymes, kinases as well as growth factors (Gerhauser, 2013). In addition, it is also reported to sensitize cancer cells to chemotherapeutic treatments (Gerhauser, 2013;Shah et al., 2015). Therefore, a certain report (Mirza et al., 2016) aimed to evaluate the effects of curcumin on CCSCs found in the peripheral blood of non-small cell lung cancer patients. ...
Circulating Cancer Stem Cells (CCSCs) constitute a distinctive category of cancer cells that play pivotal roles in shaping
multiple facets of the cancer continuum, spanning from the initiation and progression of oncogenesis and tumorigenesis to
the intricate processes of metastasis and cancer relapse. Demonstrating a unique intermediate phenotype, these specialized
cells exhibit characteristics that lie at the crossroads between epithelial and mesenchymal phenotypes.
CCSCs actively represent a rare population in the blood circulation, where their predictive and prognostic potential has
often been harnessed to gain valuable insights into the diagnosis, metastatic behavior, and recurrence patterns of cancer.
Moreover, CCSCs serve as critical indicators of a patient’s response to treatment, resistance mechanisms, and overall clinical
outcomes.
This comprehensive exploration delves into various intriguing aspects related to CCSCs, providing an in-depth analysis of
their roles and implications. The work extensively discusses the significance of CCSCs in the intricate landscape of cancer
biology, shedding light on their unique attributes and contributions to disease progression. Emphasis is placed on unraveling
the complexities surrounding CCSCs, offering a thorough and unbiased overview of the challenges associated with the
analysis of these specialized cells. In addition, a noteworthy focus of this work is directed towards the escalating importance
of CCSC-targeted cancer therapies. The implications stemming from existing research reports are thoroughly examined,
presenting a nuanced perspective on the current state of CCSC-targeted therapeutic approaches. Furthermore, the inherent
challenges in these therapeutic techniques, have also been discussed, with an effort to offer insights into future prospects and
potential advancements in the field. Overall, this work aims to contribute to the evolving landscape of cancer research by
providing a comprehensive exploration of CCSCs and their potential as targets for innovative therapeutic strategies.
... SFN, which has been identified in broccoli [11], is one of the most fascinating phytochemicals known because it protects cells under aerobic conditions from toxic carcinogens, electrophiles, and oxidants that damage DNA through the induction of the network of phase 2 detoxifying and antioxidant enzymes and the suppression of inflammatory responses [12,13]. The principal cytoprotective properties of SFN are mediated by upregulation of the transcription factor NF-E2-related factor 2 (Nrf2) and by anti-inflammatory mechanisms, such as the inhibition of the NF-κB pathway [14,15]. However, there are few reports on the efficacy of SFN in improving hepatic abnormalities in humans to date. ...
... SFN, which has been identified in broccoli [11], is one of the most fascinating phytochemicals known because it protects cells under aerobic conditions from toxic carcinogens, electrophiles, and oxidants that damage DNA through the induction of the network of phase 2 detoxifying and antioxidant enzymes and the suppression of inflammatory responses [12,13]. The principal cytoprotective properties of SFN are mediated by upregulation of the transcription factor NF-E2-related factor 2 (Nrf2) and by antiinflammatory mechanisms, such as the inhibition of the NF-κB pathway [14,15]. However, there are few reports on the efficacy of SFN in improving hepatic abnormalities in humans to date. ...
Sulforaphane (SFN) has various beneficial effects on organ metabolism. However, whether SFN affects inflammatory mediators induced by warm hepatic ischemia/reperfusion injury (HIRI) is unclear. To investigate the hepatoprotective effects of SFN using an in vivo model of HIRI and partial hepatectomy (HIRI + PH), rats were subjected to 15 min of hepatic ischemia with blood inflow occlusion, followed by 70% hepatectomy and release of the inflow occlusion. SFN (5 mg/kg) or saline was randomly injected intraperitoneally 1 and 24 h before ischemia. Alternatively, ischemia was prolonged for 30 min to evaluate the effect on mortality. The influence of SFN on the associated signaling pathways was analyzed using the interleukin 1β (IL-1β)-treated primary cultured rat hepatocytes. In the HIRI + PH-treated rats, SFN reduced serum liver enzyme activities and the frequency of pathological liver injury, such as apoptosis and neutrophil infiltration. SFN suppressed tumor necrosis factor-alpha (TNF-α) mRNA expression and inhibited nuclear factor-kappa B (NF-κB) activation by HIRI + PH. Mortality was significantly reduced by SFN. In IL-1β-treated hepatocytes, SFN suppressed the expression of inflammatory cytokines and NF-κB activation. Taken together, SFN may have hepatoprotective effects in HIRI + PH in part by inhibiting the induction of inflammatory mediators, such as TNF-α, via the suppression of NF-κB in hepatocytes.
... A recent estimate suggests that more than 40 % of global cancer related deaths may be related to malnutrition and deficiency of dietary factors (Aggarwal et al 2006). The last 20 years have witnessed a great deal of research providing evidence to show that phytochemicals are potent epigenetic regulators and can target or revert abnormal epigenetic modifications in different cancers (Gerhauser 2013). The anti-cancerous activities of these phytochemicals are attributed to their abilities to inhibit DNA methyltransferases (DNMTs), modify histones or affect the expression of non-coding RNAs (Shankar et al 2016). ...
Many phytochemicals exert anti-cancerous or cancer preventive effects on a mammalian cell by altering its epigenetic profile or the epigenome. These epigenetic signatures primarily include DNA methylation, histone modifications, non-coding RNAs and three-dimensional spatial structure of chromatin. All these epigenetic signatures also crosstalk with one another. Changes incurred by a particular phytochemical upon the cellular epigenome can be studied using various methods. These methods can be local, targeting a few known selected loci, or global, targeting the whole genome. These methods may further be divided into direct or indirect. Direct methods involve detection of individual epigenetic signatures. These methods require access to the site of modification. Chromatin immunoprecipitation (ChIP) is one of the most commonly used methods to study histone modifications. Bisulphite conversion technology is considered the gold standard in studying DNA methyl-ation. Microarray technology and RNA sequencing technology are important in studying non-coding RNA profile of the cell. The three-dimensional spatial structure of chromatin can be studied using chromosome conformation capture (3C) technology. Indirect methods include detection of different proteins or their respective mRNAs, which are responsible for carrying out specific epigenetic changes inside a cell. These methods, whether direct or indirect, have been modified variously by different workers over time. These methods are also used in combination in an integrative manner to study multiple types of epigenetic modifications together. Most of these methods are now available with high-throughput technology to generate whole-genome-based data. The present chapter provides an illustrative account of some of the most important and popular methods used to study different epigenetic signatures associated with a particular cell or tissue.
... Furthermore, AA blocks the transcription factor NF-κβ, responsible for controlling the expression of more than 400 different gene products necessary for the survival and expansion of tumor cells [72]. AA was identified as the first natural product that inhibits the activity and can be considered a natural biological compound of great value for the development of new drugs for the treatment and/or prevention of cancer [73]. More information on the biological effects of Anacardium occidentale is summarized in Table 1. ...
Neoplastic diseases are pathophysiological conditions that usually require surgical treatment, and the use of chemotherapy drugs that aim to eliminate cancer cells, however, the low toxic selectivity of these drugs can determine many devastating adverse effects. Empirically, many medicinal plants are used in the treatment of cancer, and reports of cures for this pathophysiological condition through the use of these plants have been observed in popular medicine. The present work sought to identify whether there is scientific evidence for the use of fruits and medicinal plants as a therapeutic aid in the treatment of different neoplasms, through a descriptive and exploratory review of the literature that was based both on the popular practice of using some fruits and plants medicinal products and in the scientific literature of sites such as: SciElo, Science Direct, Web of Science, PubMed and BVS (Brazilian Virtual Library). The different edible plants and vegetables presented in the present study can be considered important sources of active compounds with antineoplastic action, as they negatively modulate the progression of the development of cancer cells observed in different types of tumors.
... The basic mechanisms of epigenetics defined as the differentiation of gene expression profile without any change in DNA base sequence, are noncoding RNAs (miRNAs and long-noncoding RNAs), DNA methylation, and histone modifications. Nutri-epigenetic studies investigating the effect of diet-gene interaction in the treatment and prevention of cancers; It is stated that various natural chemo-preventive agents (micronutrients, green tea, polyphenols obtained from dietary sources, genistein and soy isoflavones, curcumin, resveratrol, dihydrocoumarin, butyrate, and nor-dihydroguaiaretic) show anticancer activities by affecting these mechanisms (Bacalini et al., 2014;Gerhauser, 2013;Kennedy et al., 2014;Pal & Tyler, 2016). ...
Cancer is the most common cause of death worldwide, following cardiovascular diseases. Cancer is a multifactorial disease and many reasons such as physical, chemical, biological, and lifestyle-related factors. Nutrition, which is one of the various factors that play a role in the prevention, development, and treatment of many types of cancer, affects the immune system, which is characterized by disproportionate pro-inflammatory signaling in cancer. Studies investigating the molecular mechanisms of this effect have shown that foods rich in bioactive compounds, such as green tea, olive oil, turmeric, and soybean play a significant role in positively changing the expression of miRNAs involved in the regulation of genes associated with oncogenic/tumor-suppressing pathways. In addition to these foods, some diet models may change the expression of specific cancer-related miRNAs in different ways. While Mediterranean diet has been associated with anticancer effects, a high-fat diet, and a methyl-restricted diet are considered to have negative effects. This review aims to discuss the effects of specific foods called "immune foods," diet models, and bioactive components on cancer by changing the expression of miRNAs in the prevention and treatment of cancer.
... Additionally, it exhibits medicinal properties such as reducing oxidative stress and significantly inhibiting damage to DNA caused by free radicals [38]. Caffeic acid is also known to prevent cancer cell growth by inhibiting the HDM histone demethylase oncoprotein gene during cancer progression [39]. Therefore, the presence of caffeic acid in the Ficus benjamina extract could contribute to its negligible cytotoxic activity towards HEK cells. ...
The study was conducted to examine the cytotoxicity of Ficus benjamina against Human Embryonic (HEK293T) cell lines. The leaves of Ficus benjamina were obtained and washed under running water, shade-dried to constant weight and ground into fine pounder, and extracted using chloroform. The chloroform extract was further separated into samples A, B, C, D, and E with the use of Thin Layer Chromatography (TLC). HEK293T cells were cultivated in DMEM or Dulbecco's Modified Eagle's Medium. The cells were then seeded at a density of 8 x 104 cells/mL in 96-well tissue culture plates, resulting in 4000 cells in 50 L of the medium in each well. With the use of the CellTitre-Glo 2.0 reagent, cytotoxicity was evaluated. In each well containing 50 liters of media, cells were treated by adding 50 liters of fresh media with a 2X concentration of the test sample and 2% DMSO, resulting in a final concentration of the test sample with 1% DMSO. After that, the treated cells were incubated for 48 hours at 37°C with 5% CO2. The luminescent signal generated was measured using a microplate luminometer with a 500 ms integration time per well. The findings from the present investigation suggest that the suppression of human embryonic kidney (HEK293T) cells by Bortezomib was markedly greater (p<0.05) in comparison to the chloroform extracts derived from Ficus benjamina leaf. However, no noteworthy distinction was observed in the cases of extract instances A, B, C, D, and E (p>0.05). The extract of Ficus benjamina exhibited selective cytotoxicity towards HEK293T cells; having minimal impact on normal cells. The study also found that the extract had a more favorable therapeutic index than the anticancer drug Bortezomib. This makes Ficus benjamina a candidate for cancer therapy research.
... Trans-resveratrol can reduce the occurrence of Ras association domain family 1 isoform A (RASSF1A) hypermethylation by inhibiting DNMT activity in women with increased breast cancer risk [31,32]. Pterostilbene is a dimethyl ether derivative of resveratrol found in blueberries, grapes, and herbs, such as Pterocarpus indicus. ...
Recently, the field of epigenetics has been intensively studied in relation to nutrition. In our study, the gene expression patterns of histone deacetylases (HDACs), which regulate the stability of histone proteins, and DNA methyltransferases (DNMTs), which regulate DNA methylation, were determined in mice. The animals were fed a human-equivalent dose of the aqueous extract of fruit seeds and peels, which is rich in flavonoids and polyphenols, for 28 days and then exposed to the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). The concentrations of trans-resveratrol and trans-piceid were determined in the consumed extract by HPLC and were 1.74 mg/L (SD 0.13 mg/L) and 2.37 mg/L (SD 0.32 mg/L), respectively, which corresponds to the consumption of 0.2–1 L of red wine, the main dietary source of resveratrol, in humans daily. Subsequently, 24 h after DMBA exposure, the expression patterns of the HDAC and DNMT genes in the liver and kidneys were determined by qRT-PCR. The DMBA-induced expression of the tested genes HDAC1, HDAC2, DNMT1, DNMT3A and DNMT3B was reduced in most cases by the extract. It has already been shown that inhibition of the DNMT and HDAC genes may delay cancer development and tumour progression. We hypothesise that the extract studied may exert chemopreventive effects.
... AITC has been found to regulate DNA methylation, a process that involves the addition of a methyl group to the DNA molecule, and can reduce DNA methylation in cancer cells. This leads to the reactivation of tumor suppressor genes and inhibition of cancer cell growth [27][28][29][30][31]. AITC has also been found to inhibit the activity of histone deacetylases (HDACs), enzymes involved in regulating histone modi cation [28, 32,33]. ...
Background: Previous studies have shown that many cruciferous vegetables have anticancer effects, which can be connected with the presence of allyl isothiocyanate (AITC). Histone demethylase KDM8 and cyclin A1 (CCNA1) were required for cell cycle G2/M progression. AITC could induce G2/M arrest of various types of human cancer cells. We aimed to validate KDM8 as a target of the antitumor effects of AITC in patient-derived tumor xenograft (PDTX) models of oral squamous cell carcinoma (OSCC).
Methods: The expression of KDM8 was assessed through tissue microarray (TMA) immunohistochemistry (IHC) assay. The effects of AITC on the expression of KDM8 and cell proliferation were investigated in OSCC cell lines, in PDTX models, and SAS subcutaneous xenograft tumors.
Results: KDM8 was overexpressed in OSCC. AITC repressed the tumor growth of OSCC PDTX and SAS subcutaneous xenograft. Furthermore, AITC downregulated the expression of KDM8 and CCNA1 and induced histone H3K36me2 expression in oral cancer cells.
Conclusions: AITC exerts anticancer effects on oral cancer by inducing cell cycle arrest via inhibiting the KDM8-CCNA1 axis.
... For a long time, they have been used for the protection and treatment of various diseases, such as diabetic nephropathy (Hudlikar et al., 2021), obesity (Martin et al., 2013;Dincer and Yuksel, 2021;Li et al., 2022c), and cancer (Lee et al., 2011;Kotecha et al., 2016). In general, mounting evidence shows that dietary phytochemicals are potent chemopreventive/cancer interceptive agents due to their antioxidant, metabolic modulation, and epigenetic regulation properties (Gerhauser, 2013;Thakur et al., 2014;Russo et al., 2017;Wu et al., 2022). In this review, we will discuss the potential cancer interceptive effects of dietary phytochemicals by targeting metabolic rewiring and epigenetic reprogramming in cancer. ...
Metabolic rewiring and epigenetic reprogramming are closely inter-related, and mutually regulate each other to control cell growth in cancer initiation, promotion, progression, and metastasis. Epigenetics plays a crucial role in regulating normal cellular functions as well as pathological conditions in many diseases, including cancer. Conversely, certain mitochondrial metabolites are considered as essential cofactors and regulators of epigenetic mechanisms. Furthermore, dysregulation of metabolism promotes tumor cell growth and reprograms the cells to produce metabolites and bioenergy needed to support cancer cell proliferation. Hence, metabolic reprogramming which alters the metabolites/epigenetic cofactors, would drive the epigenetic landscape, including DNA methylation and histone modification, that could lead to cancer initiation, promotion, and progression. Recognizing the diverse array of benefits of phytochemicals, they are gaining increasing interest in cancer interception and treatment. One of the significant mechanisms of cancer interception and treatment by phytochemicals is reprogramming of the key metabolic pathways and remodeling of cancer epigenetics. This review focuses on the metabolic remodeling and epigenetics reprogramming in cancer and investigates the potential mechanisms by which phytochemicals can mitigate cancer.
... The benefits of taxol used as a cancer chemopreventive agent are evidenced in several bioassays. For example, investigations on epigenetics 81 and signaling routes, 82 and Keap1-Nrf2-ARE have emerged as useful methods in the identification of cell defense and survival. [83][84][85] Some assays targeting the initiation, promotion, and propagation phases of carcinogenesis are being performed. ...
This work briefly reviews cancer chemoprevention. This is a very challenging field, as products with a high level of toxicity such as chemotherapeutic agents may be proposed and accepted only under life-threatening conditions. Cancer chemoprevention is otherwise limited to completely safe substances, preferably having neither toxic nor side effects, administered in relatively low amounts. Phases of clinical trials, therapeutic end-points, and biomarkers of chemoprevention are difficult to be defined. The clinical trials needed to prove the efficacy of chemopreventive agents must be very long and extremely widespread to achieve significance, with many variables difficult to control, and therefore subjected to many confounding factors. This makes them almost impossible. It is, therefore, no surprise, if the progress of chemoprevention has been so far very limited. There are only a few examples of direct use of chemopreventive agents, under investigation, but with anything but established protocols, in addition to indirect uses such as general supplementation with antioxidant, anti-inflammatory, and immune-supportive agents. Cancer chemoprevention remains a potentially very rewarding approach, certainly worth further study, but extremely difficult to pursue, in need of different methodological approaches to producing valuable chemopreventive compounds of clear dosages and benefits.
