Melatonin for gastric cancer treatment: where do we stand?

Gastric cancer (GC) is the third leading reason of death in men and the fourth in women. Studies have documented an inhibitory function of melatonin on the proliferation, progression and invasion of GC cells. MicroRNAs (miRNAs) are small, non-coding RNAs that play an important function in regulation of biological processes and gene expression of the cells. Some studies reported that melatonin can suppress the progression of GC by regulating the exosomal miRNAs. Thus, melatonin represents a promising potential therapeutic agent for subjects with GC. Herein, we evaluate the existing data of both in vivo and in vitro studies to clarify the molecular processes involved in the therapeutic effects of melatonin in GC. The data emphasize the critical function of melatonin in several signaling ways by which it may inhibit cancer cell proliferation, decrease chemo-resistance, induce apoptosis as well as limit invasion, angiogenesis, and metastasis. This review provides a resource that identifies some of the mechanisms by which melatonin controls GC enlargement. In light of the findings, melatonin should be considered a novel and testable therapeutic mediator for GC treatment.

Programmed cell death and melatonin: A comprehensive review.

Melatonin (MLT), a main product of pineal gland, recently has attracted the attention of scientists due to its benefits in various diseases and also regulation of cellular homeostasis. Its receptor scares widely distributed indicating that it influences numerous organs. Programmed cell death (PCD), of which there several types, is a regulated by highly conserved mechanisms and important for development and function of different organs. Enhancement or inhibition of PCDs could be a useful technique for treatment of different diseases and MLT, due to its direct effects on these pathways, is a good candidate for this strategy. Many studies investigated the role of MLT on PCDs in different diseases and in this review, we summarized some of the most significant studies in this field to provide a better insight into the mechanisms of modulation of PCD by MLT modulation.

Potential Diagnostic Value of Abnormal Pyroptosis Genes Expression in Myelodysplastic Syndromes (MDS): A Primary Observational Cohort Study.

Background: Myelodysplastic syndromes (MDS) are determined by ineffective hematopoiesis and bone marrow cytological dysplasia with somatic gene mutations and chromosomal abnormalities. Accumulating evidence has revealed the pivotal role of NLRP3 inflammasome activation and pyroptotic cell death in the pathogenesis of MDS. Although MDS can be diagnosed with a variety of morphologic and cytogenetic tests, most of these tests have limitations or problems in practice. Materials and Methods: In the present study, we evaluated the expression of genes that form the inflammasome (NLRP3, ASC, and CASP1) in bone marrow specimens of MDS patients and compared the results with those of other leukemias to evaluate their diagnostic value for MDS. Primary samples of this observational cohort study were collected from aspiration samples of patients with myelodysplastic syndromes (27 cases) and patients with non-myelodysplastic syndrome hematological cancers (45 cases). After RNA extraction and c.DNA synthesis, candidate transcripts and housekeeping transcripts were measured by real-time PCR method (SYBER Green assay). Using Kruskal-Wallis the relative gene expressions were compared and differences with p value less than 0.05 were considered as significant. Discrimination capability, cut-off, and area under curve (AUC) of all markers were analyzed with recessive operation curve (ROC) analysis. Results: We found that Caspase-1 and ASC genes expressed at more levels in MDS specimens compared to non-MDS hematological malignancies. A relative average expression of 10.22 with a p-value of 0.001 and 1.86 with p=0.019 was detected for Caspase-1 and ASC, respectively. ROC curve analysis shows an AUC of 0.739 with p=0.0001 for Caspase-1 and an AUC of 0.665 with p=0.0139 for ASC to MDS discrimination. Conclusion: Our results show that Caspase-1 and ASC gene expression levels can be used as potential biomarkers for MDS diagnosis. Prospective studies with large sample numbers are suggested.

Melatonin affects the expression of microRNA-21: A mini-review of current evidence.

Melatonin (MLT) is an endogenous hormone produced by pineal gland which possess promising anti-tumor effects. Anti-inflammatory and anti-oxidant properties of MLT, along with its immunomodulatory, proapoptotic, and anti-angiogenic properties, are often referred to the main mechanisms of its anti-tumor effects. Recent evidence has suggested that epigenetic alterations are also involved in the anti-tumor properties of MLT. Among these MLT-induced epigenetic alterations is modulation of the expression of several oncogenic and tumor suppressor microRNAs(miRNAs). MiRNAs are among the most promising and potential therapeutic and diagnostic tools in different diseases and enhanced the development of better therapeutic drugs. Suppression of oncomicroRNAs such as microRNA-21, - 20a, and - 27a as well as, up-regulation of microRNA-34 a/c are among the most important effects of MLT on microRNAs homeostasis. Recently, miR-21 has attracted the attention of scientists due to the its wide range of effects on different cancers and diseases. Regulation of this RNA may be a key to the development of better therapeutic targets. The present review will summarize the findings of in vitro and experimental studies of MLT-induced impacts on the expression of microRNAs which are involved in different models and numerous stages of tumor initiation, growth, metastasis, and chemo-resistance.

The therapeutic effects of berberine for gastrointestinal cancers.

Cancer is one of the most serious human health issues. Drug therapy is the major common way to treat cancer. There is a growing interest in using natural compounds to overcome drug resistance, adverse reactions, and target specificity of certain types of drugs that may affect several targets with fewer side effects and be beneficial against various types of cancer. In this regard, the use of herbal medicines alone or in combination with the main anticancer drugs is commonly available. Berberine (BBR), a nature-driven phytochemical component, is a well-known nutraceutical due to its wide variety of pharmacological activities, including antioxidant, anti-inflammatory, antibacterial, antifungal, antiparasitic, antidiabetic, antihypertensive, and hypolipidemic. In addition, BBR exerts anticancer activities. In present article, we summarized the information available on the therapeutic effects of BBR and its mechanisms on five types of the most prevalent gastrointestinal cancers, including esophageal, gastric, colorectal, hepatocarcinoma, and pancreatic cancers.

Melatonin as a Promising Agent for Cancer Treatment: Insights into its Effects on the Wnt/beta-catenin Signaling Pathway.

In recent years, substantial advances have been made in cancer treatment modalities. Yet, within the last three decades, neither cancer incidence nor the cancer-induced mortality rate has changed. Available anti-cancer chemotherapeutics possess remarkably restricted effectiveness and often have severe adverse effects. Hence, the identification of novel pharmaceutical agents that do not exhibit these major disadvantages is imperative. Melatonin, an important endogenous molecule synthesized and secreted by the pineal gland, is a promising chemical agent that has been comprehensively assessed over the last decades for its anti-inflammatory and anti-cancer properties. Melatonin is reportedly a significant inhibitor of cancer initiation, progression, and metastasis. The anti-- cancer potential of melatonin is principally mediated by reversing the up-regulated amounts of different transcription factors, growth factors, inflammatory cytokines, protein kinases, and other oncogenic agents. Also, melatonin often has signifcant inhibitory effects on cancer cell proliferation through either promoting apoptosis or inducing cell cycle arrest. The current review provides an insight into melatonin-induced effects against various human cancers with a particular focus on the regulation of Wnt/ß-catenin signaling pathway.

Modulation of Long Non-coding RNAs and MicroRNAs by Quercetin as a Potential Therapeutical Approach in Cancer: A Comprehensive Review.

Cancer can take years to develop, both at its beginning and during its development. All typical epithelial cancers have a long latency period, sometimes 20 years or more, and if they are clinically detected, distinct genes may include infinite mutations. Long non-coding RNAs (LncRNAs) are a subset of RNAs that regulate many biological processes, including RNA processing, epigenetic control, and signal transduction. Current studies show that lncRNAs, which are dysregulated in cancer, play a significant function in the growth and spread of the illness. LncRNAs have been connected to the overexpression of specific proteins that function in tumors' spread and growth. Moreover, through translational inhibition, microRNAs (miRNAs) regulates gene expression sequence specifically. Apart from that, non-coding RNAs known as miRNAs, with a length of around 22 nucleotides, controls gene expressions in a sequence-specific way either by preventing translation or degrading messenger RNA (mRNA). Quercetin appears to have a significant role in altering miRNA and lncRNA expression, which is linked to variations in the production of oncogenes, tumor suppressors, and proteins produced from cancer. Quercetin may change the earliest epigenetic modifications related to cancer prevention in addition to its usual antioxidant or anti-inflammatory effects. It would be beneficial to have more in-depth information on how Quercetin modulates miRNAs and lncRNAs to use it as a cancer therapeutic strategy. Here, we go through what is known about Quercetin's potential to modulate miRNAs and lncRNAs in various malignancies.

Potential Drug Interactions in Terminally-Ill Cancer Patients, a Report from the Middle East.

This study aims to evaluate the epidemiology of potential drug interactions in terminally-ill cancer patients receiving exclusively supportive care. In this cross-sectional study, during a 6-month follow-up, we considered the medical record of terminally-ill cancer patients referred to palliative care at the cancer center in Isfahan, Iran. Potential drug-drug interactions (DDIs) were assessed by Lexi-Interact ver.1.1 online software. During the study period, 133 terminally-ill cancer patients were recruited. We detected 1678 DDIs with moderate or major severity levels. Among them, 330, 219, 32, 1075, and 51 interactions were categorized in B, C, D, and X drug interactions categories, respectively. One hundred and twenty-two patients (91.73%) encountered at least one potential drug-drug interaction during the end of life care. Mechanistically, most drug-drug interactions (64.5%) were pharmacodynamics. The most frequent pharmacological class of drugs responsible for DDIs were quetiapine (91 cases), oxycodone (87 cases), and sertraline (55 cases). Interaction between oxycodone and sertraline was found to be in the top 10 detected DDIs (13.7%). Our results showed that potentially moderate or major drug-drug interactions often occur among terminally-ill cancer patients and the clinical significance of DDIs should be considered meticulously in the palliative care cancer setting.

The molecular perspective on the melanoma and genome engineering of T-cells in targeting therapy.

Melanoma, an aggressive malignant tumor originating from melanocytes in humans, is on the rise globally, with limited non-surgical treatment options available. Recent advances in understanding the molecular and cellular mechanisms underlying immune escape, tumorigenesis, drug resistance, and cancer metastasis have paved the way for innovative therapeutic strategies. Combination therapy targeting multiple pathways simultaneously has been shown to be promising in treating melanoma, eliciting favorable responses in most melanoma patients. CAR T-cells, engineered to overcome the limitations of human leukocyte antigen (HLA)-dependent tumor cell detection associated with T-cell receptors, offer an alternative approach. By genetically modifying apheresis-collected allogeneic or autologous T-cells to express chimeric antigen receptors, CAR T-cells can appreciate antigens on cell surfaces independently of major histocompatibility complex (MHC), providing a significant cancer cell detection advantage. However, identifying the most effective target antigen is the initial step, as it helps mitigate the risk of toxicity due to "on-target, off-tumor" and establishes a targeted therapeutic strategy. Furthermore, evaluating signaling pathways and critical molecules involved in melanoma pathogenesis remains insufficient. This study emphasizes the novel approaches of CAR T-cell immunoediting and presents new insights into the molecular signaling pathways associated with melanoma.

Circular RNAs: pivotal role in the leukemogenesis and novel indicators for the diagnosis and prognosis of acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy and affected patients have poor overall survival (OS) rates. Circular RNAs (circRNAs) are a novel class of non-coding RNAs (ncRNAs) with a unique loop structure. In recent years, with the development of high-throughput RNA sequencing, many circRNAs have been identified exhibiting either up-regulation or down-regulation in AML patients compared with healthy controls. Recent studies have reported that circRNAs regulate leukemia cell proliferation, stemness, and apoptosis, both positively and negatively. Additionally, circRNAs could be promising biomarkers and therapeutic targets in AML. In this study, we present a comprehensive review of the regulatory roles and potentials of a number of dysregulated circRNAs in AML.

Modulation of long non-coding RNAs by resveratrol as a potential therapeutic approach in cancer: A comprehensive review.

LncRNAs, or long non-coding RNAs, are a subset of RNAs that play a regulatory role in a wide range of biological functions, including RNA processing, epigenetic regulation, and signal transduction. Recent research indicates that lncRNAs play a key role in the development and spread of cancer by being dysregulated in the disease. In addition, lncRNAs have been linked to the overexpression of certain proteins that are involved in tumor development and progression. Resveratrol has anti-inflammatory and anti-cancer properties that it exerts through regulating different lncRNAs. By the regulation of tumor-supportive and tumor-suppressive lncRNAs, resveratrol acts as an anti-cancer agent. By downregulating the tumor-supportive lncRNAs DANCR, MALAT1, CCAT1, CRNDE, HOTAIR, PCAT1, PVT1, SNHG16, AK001796, DIO3OS, GAS5 and H19, and upregulating MEG3, PTTG3P, BISPR, PCAT29, GAS5, LOC146880, HOTAIR, PCA3, NBR2, this herbal remedy causes apoptosis and cytotoxicity. For the purpose of using polyphenols in cancer therapy, it would be helpful to have more in-depth knowledge about lncRNA modulation via resveratrol. Here, we discuss the current knowledge and future promise of resveratrol as modulators of lncRNAs in different cancers.

Efficacy of plasmapheresis in neutropenic patients suffering from cytokine storm because of severe COVID-19 infection.

Background: With the emergence of the coronavirus disease 2019 (COVID-19) and inability of healthcare systems to control the disease, various therapeutic theories with controversial responses have been proposed. Plasmapheresis was administered as a medication. However, the knowledge of its efficacy and indications is inadequate. This study evaluated the use of plasmapheresis in critically ill patients with cancer. Methods: This randomized clinical trial was conducted on 86 patients with malignancies, including a control group (N=41) and an intervention group (N=45) with severe COVID-19 during 2020-21. Both groups were treated with routine medications for COVID-19 management according to national guidelines, and plasmapheresis was applied to the intervention group. C-reactive protein (CRP), D-dimer, ferritin, lactate dehydrogenase, hemoglobin, and white blood cell, polymorphonuclear, lymphocyte, and platelet levels were measured at admission and at the end of plasmapheresis. Other variables included neutrophil recovery, intensive care unit admission, intubation requirements, length of hospital stay, and hospitalization outcomes. Results: CRP(P<0.001), D-dimer (P<0.001), ferritin (P=0.039), and hemoglobin (P=0.006) levels were significantly different between the groups after the intervention. Neutrophil recovery was remarkably higher in the case than in the control group (P<0.001). However, plasmapheresis did not affect the length of hospital stay (P=0.076), which could have significantly increased survival rates (P<0.001). Conclusion: Based on the study findings, plasmapheresis led to a significant improvement in laboratory markers and survival rate in patients with severe COVID-19. These findings reinforce the value of plasmapheresis in cancer patients as a critical population suffering from neutropenia and insufficient immune responses.

A systematic review evaluating the efficacy of autologous hematopoietic transplantation for diffuse large B cell lymphoma-type Richter syndrome.

Background: Chronic lymphocytic leukemia (CLL) can transform into fast growing lymphoma for diffuse large B-cell lymphoma (DLBCL) called Richter's syndrome (RS), which is commonly related to an existence of large B-cells with equal or larger size than macrophage nuclei or more than twice those of normal lymphocyte. We conducted a systematic review of the existing literature to assess the clinical efficacy of auto-HCT for patients with RS. Methods: We searched 4 main databases; EMBASE, Google Scholar, Scopus, PubMed and Web of Science and was done on December 26, 2021. All analyses in this study were performed by Stata software and this review was reported in accordance with PRISMA 2020. Results: Data was extracted from 4 articles; the total number of patients was reported to be 110. Based on the meta-analysis findings, pooled overall survival rate was 56.36% (95%CI= (46.98-65.31). In figure 2, the forest plot of combined results is shown. Conclusion: Despite the use of common treatment regimens such as chemo immunotherapy and the availability of novel therapies including B-cell receptor inhibitors and rituximab-cyclophosphamide-hydroxydaunorubicin-Oncovin-prednisone (CHOP-R) regimen, the status of disease progression and recovery in RS cases is still not strong enough.

Therapeutic effects of melatonin on endometriosis, targeting molecular pathways: Current knowledge and future perspective.

Endometriosis, the very serious disease in women creates a huge financial burden worldwide, which is comparable to diabetes mellitus. In addition to the typical pelvic pain, endometriosis is related to low life quality and decreased work efficiency; clinical consequences include mood complaints, metabolic impairments, inflammation, immunologic problems, and elevated malignancy risks. Several risk factors are correlated with endometriosis including elevated oxidative and nitrosative stress, long-lasting inflammation, raised immune tolerance, as well as autoimmunity. Melatonin is a natural molecule present throughout both the plant and animal kingdoms. It has numerous functions as an antioxidant and anti-inflammatory agent. Due to the anti-proliferative, antioxidant, anti-inflammatory, and anti-invasive features of melatonin, it performances as a beneficial agent to limit endometriosis; this involves several pathways including antiestrogenic, antioxidant, anti-inflammatory, and anti-apoptosis effects, as well as reducing the growth of E2-induced endometriotic tissue. Moreover, melatonin can favor sleep quality and decrease the unwanted signs in the patients. However, most of the data on melatonin accured from experimental works and additional clinical trials are needed. This review summarizes what is currently known regarding the influence of melatonin on endometriosis. AVAILABILITY OF DATA AND MATERIAL: Not applicable.

Species distribution and susceptibility profiles of oral candidiasis in hematological malignancy and solid tumor patients.

Oral colonization and infection by Candida species are common in cancer patients receiving chemoradiotherapy, which has significantly increased in recent years. This study aimed to evaluate the frequency, distribution, and antifungal susceptibility profiles of Candida species isolates in patients with hematological malignancy and solid tumors. This study was conducted on a total of 45 cancer patients undergoing treatment with concurrent chemoradiotherapy within 2019-2020. The identification of Candida species was accomplished based on conventional examination and molecular assays. The minimum inhibitory concentrations were determined based on the guidelines of Clinical and Laboratory Standards Institute. The highest prevalence rates of oral candidiasis were observed in patients with chronic lymphoid leukemia (24.4%) and lymphoma (20%). The majority of the patients had oral candidiasis caused by non-albicans Candida species (64.4%). The results of the multiplex PCR for the identification of Candida glabrata, Candida nivariensis, Candida bracarensis, and species-specific Candida parapsilosis complex showed that all isolate amplification products at 397 bp and 171 bp were related to C. glabrata and C. parapsilosis, respectively. There was a significant difference in the Candida species distribution between the hematological malignancies and solid tumors patients. The results of MIC showed that clotrimazole, voriconazole, and caspofungin were the most effective antifungal drugs against oral non-Candida albicans isolates. An understanding of the epidemiology of oral candidiasis among hematological malignancies and solid tumors patients is currently imperative to guide optimal empirical treatment strategies for affected patients.

Curcumin supplementation prevents cisplatin-induced nephrotoxicity: a randomized, double-blinded, and placebo-controlled trial.

Background and purpose: Cisplatin-induced nephrotoxicity (CIN) remains the most prevailing unfavorable influence and may affect its clinical usage. This study sought to explore the possible impacts of curcumin on preventing CIN in human subjects. Clinical design: The investigation was a placebo-controlled, double-blinded, randomized clinical trial conducted on 82 patients receiving nano-curcumin (80 mg twice daily for five days) or an identical placebo with standard nephroprotective modalities against CIN. Data was gathered on patients' demographics, blood, urinary nitrogen, creatinine (Cr) levels, urinary electrolytes, and urine neutrophil gelatinase-associated lipocalin (NGAL) levels in treatment and placebo groups, 24 h and five days after initiating the administration of cisplatin. Findings/Results: Both investigation groups were alike considering the demographic characteristics and clinical baseline data. Curcumin administration led to a significant improvement in blood-urine nitrogen (BUN). BUN, Cr, glomerular filtration rate (GFR), and the ratio of NGAL-to-Cr considerably altered during the follow-up periods. However, the further alterations in other indices, including urinary sodium, potassium, magnesium, NGAL values, and potassium-to-Cr ratio were not statistically noteworthy. The significant differences in the NGAL-to-Cr ratio between the two groups may indicate the potential protective impact of curcumin supplementation against tubular toxicity. Curcumin management was safe and well-accepted; only insignificant gastrointestinal side effects were reported. Conclusion and implications: Curcumin supplementation may have the potential to alleviate CIN and urinary electrolyte wasting in cancer patients. Future research investigating the effects of a longer duration of follow-up, a larger participant pool, and a higher dosage of curcumin are recommended.

Potential Drug Interactions in Hospitalized Hematologic Cancer Patients: New Update with New Chemotherapy Regimens.

Objective: This cross-sectional study aimed to assess the frequency of potential drug-drug interactions (DDIs) and demographic correlates of moderate and major DDIs among patients with hematologic cancer at a referral hematology hospital in Iran. Methods: In this study, for 6 months, all patients suffering from hematologic cancers admitted to the tertiary oncology hospital, Omid, Isfahan, were considered. Data from all medications prescribed to patients during hospitalization were analyzed using the online Lexicomp® drug interaction checker, recording all interactions classified by risk level: C, D, or X. Findings: A total of 674 DDIs were detected in 109 patients. The prevalence of treatments with at least one clinically relevant interaction was 95%, being 57.9% for those at level C and 31.5% for levels D and X. According to the frequency, the main interaction was between aprepitant and corticosteroids, followed by the interaction between aprepitant and vincristine. The most common interaction between antineoplastic agents was between doxorubicin and cyclophosphamide. In terms of mechanism, most of DDIs (54.9%) were pharmacodynamics. Only the number of administered medications was associated with DDI occurrence. Conclusion: Potential DDIs of moderate to major severity are common among patients with hematologic malignancies. This underscores the importance of implementing different strategies to mitigate this clinically significant risk.

Performance Challenges in a Newly Established Clean Room at Omid Hospital, Isfahan, Iran: A Descriptive Study.

Objective: This study aimed to comprehensively assess the challenges faced by a newly established clean room in the oncology center of Omid Hospital, Isfahan, Iran, one of the first of its kind in the country. The research also sought to identify the underlying causes of these challenges and propose potential solutions to address them. Methods: A 6-month cross-sectional study was conducted from December 2021 to May 2022. International guidelines such as British Columbia Cancer Agencies' guideline of hazardous drugs, the National Institute for Occupational Safety and Health guideline for working with hazardous drugs, and United States pharmacopeia related to cleanroom performance were studied, translated, and summarized into a checklist. The staff performance in Omid Hospital's clean room was compared to the data collection form, and all medication errors were documented and analyzed. The study also explained the underlying causes of these challenges and proposed potential solutions. Findings: Among 1005 chemotherapy regimens, 836 errors were detected, stemming from issues such as engineering and construction challenges, lack of human resources and essential equipment, and budgetary constraints. Conclusion: Despite the involvement of a trained oncology clinical pharmacist, Omid Hospital's cleanroom faces significant challenges within the medical and hospital system, leading to non-standard challenges. The study recommends multidisciplinary approaches in the hospital to mitigate these challenges and improve cleanroom performance.

Clinical characteristics of COVID-19-infected cancer patients, Isfahan, Iran.

Background: Cancer patients, as a highly vulnerable population, are receiving a great deal of attention in the current crisis of coronavirus 2019 (COVID-19). To date, shreds of evidence are not sufficient to the description of COVID-19 outcomes in patients with cancer. This study was performed to evaluate the demographic and clinical characteristics and subsequent outcomes of COVID-19 in cancer patients. Materials and Methods: A hospital-based study was conducted involving 66 cancer patients with a confirmed diagnosis of COVID-19 from January 15, 2020, to December 21, 2020, in Isfahan, Iran. The clinical information was collected by interview and medical records. The statistical analyses were performed to describe categorical variables as well as mean, standard deviation, median, and the interquartile range for quantitative variables. Results: In our study, 66 cancer patients with confirmed COVID-19 (age: 17-97 years; 50% female) were included. Leukemia and bone marrow cancer with a frequency of 25.7% were the most common types of cancer among them. Cancer patients mostly complained of fever, cough and fatigue, and shortness of breath. Among 76.9% of patients discharged from the hospital with relative recovery, 23% died; the most common cause of death was acute respiratory distress syndrome. Age, gender, and type of cancer did not affect cancer mortality. COVID-19 had no potential effect to increase the risk of side effects of anticancer therapies. Conclusion: The results of our studies revealed that cancer is an important risk factor for the higher rate of mortality in patients with COVID-19. These findings could help physicians for the management, treatment, and supportive care of COVID-19 cancer patients.

The role of dietary polyphenols in alternating DNA methylation in cancer.

Natural products such as curcumin, quercetin, and resveratrol have been shown to have antitumor effectsand several studies have examined their role in treating cancer, either alone or in combination with other chemotherapeutic drugs. These compounds are capable of affecting different cancer-related mechanisms, such as proliferation, inflammation, invasion, and metastasis. Along with all of the benefits of these agents, affecting epigenetic processes is one of the most important aspects of their impact. Epigenetic modifications can be categorized into three main processes that include DNA methylation, histone modification, and regulation of small non-coding RNAs. Therefore, targeting DNA methylation can be used as a cancer treatment strategy by identifying or developing methylation modulators. Herein, we take a look into the studies investigating the role of natural products (e.g. curcumin, resveratrol, epigallocatechin gallate (EGCG), and quercetin) in alternating the DNA methylation status of various cancer cells. We discuss how these compounds reduce the expression of enzymes mediating the methylation of tumor suppressor genes and thereby, increasing the expression of tumor suppressors while reactivating antitumor signaling pathways.