Given the stochastic complexity of cancer diseases, the development of chemotherapeutic drugs is almost limited by problems of selectivity and side effects. Furthermore, an increasing number of protective approaches have been recently considered as the main way to limit these pathologies. Natural bioactive compounds, and particularly dietary phenolic compounds, showed major protective and therapeutic effects against different types of human cancers. Indeed, phenolic substances have functional groups that allow them to exert several anti-cancer mechanisms, such as the induction of apoptosis, autophagy, cell cycle arrest at different stages, and the inhibition of telomerase. In addition, in vivo studies show that these phenolic compounds also have anti-angiogenic effects via the inhibition of invasion and angiogenesis. Moreover, clinical studies have already highlighted certain phenolic compounds producing clinical effects alone, or in combination with drugs used in chemotherapy. In the present work, we present a major advance in research concerning the mechanisms of action of the different phenolic compounds that are contained in food medicinal plants, as well as evidence from the clinical trials that focus on them.
Alzheimer's disease remains one of the most widespread neurodegenerative reasons for dementia worldwide and is associated with considerable mortality and morbidity. Therefore, it has been considered a priority for research. Indeed, several risk factors are involved in the complexity of the therapeutic ways of this pathology, including age, traumatic brain injury, genetics, exposure to aluminum, infections, diabetes, vascular diseases, hypertension, dyslipidemia, and obesity. The pathophysiology of Alzheimer's disease is mostly associated with hyperphosphorylated protein in the neuronal cytoplasm and extracellular plaques of the insoluble β-amyloid peptide. Therefore, the management of this pathology needs the screening of drugs targeting different pathological levels, such as acetylcholinesterase (AchE), amyloid β formation, and lipoxygenase inhibitors. Among the pharmacological strategies used for the management of Alzheimer's disease, natural drugs are considered a promising therapeutic strategy. Indeed, bioactive compounds isolated from different natural sources exhibit important anti-Alzheimer effects by their effectiveness in promoting neuroplasticity and protecting against neurodegeneration as well as neuroinflammation and oxidative stress in the brain. These effects involve different sub-cellular, cellular, and/or molecular mechanisms, such as the inhibition of acetylcholinesterase (AchE), the modulation of signaling pathways, and the inhibition of oxidative stress. Moreover, some nanoparticles were recently used as phytochemical delivery systems to improve the effects of phytochemical compounds against Alzheimer's disease. Therefore, the present work aims to provide a comprehensive overview of the key advances concerning nano-drug delivery applications of phytochemicals for Alzheimer's disease management.
BACKGROUND: Screening new natural molecules with pharmacological and/or cosmetic properties remains a highly sought-after area of research. Moreover, essential oils and volatile compounds have recently garnered significant interest as natural substance candidates. In this study, the volatile components of Pistacia lentiscus L. essential oils (PLEOs) isolated from the fruit and its main compounds, alpha-pinene, and limonene, are investigated for antioxidant, antidiabetic, and dermatoprotective activities.
METHODS: In vitro antioxidant activity was investigated using 2,2'-diphenyl-1-picrylhydrazyl (DPPH), fluorescence recovery after photobleaching (FRAP), and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) methods. The antidiabetic and dermatoprotective effects were studied using enzyme inhibitory activities.
RESULTS: Antioxidant tests showed that PLEO has the best activity (ranging from 29.64 ± 3.04 to 73.80 ± 3.96 µg/mL) compared to its main selected molecules (ranging from 74 ± 3.72 to 107.23 ± 5.03 µg/mL). The α-glucosidase and α-amylase assays demonstrated that the elements tested have a promising antidiabetic potential with IC50values ranging from 78.03 ± 2.31 to 116.03 ± 7.42 µg/mL and 74.39 ± 3.08 to 112.35 ± 4.92 µg/mL for the α-glucosidase and α-amylase assays, respectively, compared to the standard drug. For the tyrosinase test, we found that the EOs (IC50 = 57.72 ± 2.86 µg/mL) followed by limonene (IC50 = 74.24 ± 2.06 µg/mL) and α-pinene (IC50 = 97.45 ± 5.22 µg/mL) all exhibited greater inhibitory effects than quercetin (IC50 = 246.90 ± 2.54 µg/mL).
CONCLUSIONS: Our results suggest that the biological activities of PLEO, as well as its main compounds, make them promising candidates for the development of new strategies aimed at improving dermatoprotection and treating diseases associated with diabetes mellitus and oxidative stress.
Panobinostat, also known as Farydak®, LBH589, PNB, or panobinostat lactate, is a hydroxamic acid that has been approved by the Food and Drug Administration (FDA) for its anti-cancer properties. This orally bioavailable drug is classified as a non-selective histone deacetylase inhibitor (pan-HDACi) that inhibits class I, II, and IV HDACs at nanomolar levels due to its significant histone modifications and epigenetic mechanisms. A mismatch between histone acetyltransferases (HATs) and HDACs can negatively affect the regulation of the genes concerned, which in turn can contribute to tumorigenesis. Indeed, panobinostat inhibits HDACs, potentially leading to acetylated histone accumulation, re-establishing normal gene expression in cancer cells, and helping to drive multiple signaling pathways. These pathways include induction of histone acetylation and cytotoxicity for the majority of tested cancer cell lines, increased levels of p21 cell cycle proteins, enhanced amounts of pro-apoptotic factors (such as caspase-3/7 activity and cleaved poly (ADP-ribose) polymerase (PARP)) associated with decreased levels of anti-apoptotic factors [B-cell lymphoma 2 (Bcl-2) and B-cell lymphoma-extra-large (Bcl-XL)], as well as regulation of immune response [upregulated programmed death-ligand 1 (PD-L1) and interferon gamma receptor 1 (IFN-γR1) expression] and other events. The therapeutic outcome of panobinostat is therefore mediated by sub-pathways involving proteasome and/or aggresome degradation, endoplasmic reticulum, cell cycle arrest, promotion of extrinsic and intrinsic processes of apoptosis, tumor microenvironment remodeling, and angiogenesis inhibition. In this investigation, we aimed to pinpoint the precise molecular mechanism underlying panobinostat's HDAC inhibitory effect. A more thorough understanding of these mechanisms will greatly advance our knowledge of cancer cell aberrations and, as a result, provide an opportunity for the discovery of significant new therapeutic perspectives through cancer therapeutics.
Romidepsin, also known as NSC630176, FR901228, FK-228, FR-901228, depsipeptide, or Istodax®, is a natural molecule produced by the Chromobacterium violaceum bacterium that has been approved for its anti-cancer effect. This compound is a selective histone deacetylase (HDAC) inhibitor, which modifies histones and epigenetic pathways. An imbalance between HDAC and histone acetyltransferase can lead to the down-regulation of regulatory genes, resulting in tumorigenesis. Inhibition of HDACs by romidepsin indirectly contributes to the anticancer therapeutic effect by causing the accumulation of acetylated histones, restoring normal gene expression in cancer cells, and promoting alternative pathways, including the immune response, p53/p21 signaling cascades, cleaved caspases, poly (ADP-ribose) polymerase (PARP), and other events. Secondary pathways mediate the therapeutic action of romidepsin by disrupting the endoplasmic reticulum and proteasome and/or aggresome, arresting the cell cycle, inducing intrinsic and extrinsic apoptosis, inhibiting angiogenesis, and modifying the tumor microenvironment. This review aimed to highlight the specific molecular mechanisms responsible for HDAC inhibition by romidepsin. A more detailed understanding of these mechanisms can significantly improve the understanding of cancer cell disorders and pave the way for new therapeutic approaches using targeted therapy.
Cancer progression is strongly affected by epigenetic events in addition to genetic modifications. One of the key elements in the epigenetic control of gene expression is histone modification through acetylation, which is regulated by the synergy between histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDACs are thought to offer considerable potential for the development of anticancer medications, particularly when used in conjunction with other anticancer medications and/or radiotherapy. Belinostat (Beleodaq, PXD101) is a pan-HDAC unsaturated hydroxamate inhibitor with a sulfonamide group that has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of refractory or relapsed peripheral T-cell lymphoma (PTCL) and solid malignancies or and other hematological tissues. This drug modifies histones and epigenetic pathways. Because HDAC and HAT imbalance can lead to downregulation of regulatory genes, resulting in tumorigenesis. Inhibition of HDACs by belinostat indirectly promotes anti-cancer therapeutic effect by provoking acetylated histone accumulation, re-establishing normal gene expressions in cancer cells and stimulating other routes such as the immune response, p27 signaling cascades, caspase 3 activation, nuclear protein poly (ADP-ribose) polymerase-1 (PARP-1) degradation, cyclin A (G2/M phase), cyclin E1 (G1/S phase) and other events. In addition, belinostat has already been discovered to increase p21WAF1 in a number of cell lines (melanoma, prostate, breast, lung, colon, and ovary). This cyclin-dependent kinase inhibitor actually has a role in processes that cause cell cycle arrest and apoptosis. Belinostat's clinical effectiveness, comprising Phase I and II studies within the areas of solid and hematological cancers, has been evidenced through several investigative trials that have supported its potential to be a valuable anti-cancer drug. The purpose of this research was to provide insight on the specific molecular processes through which belinostat inhibits HDAC. The ability to investigate new therapeutic options employing targeted therapy and acquire a deeper understanding of cancer cell abnormalities may result from a better understanding of these particular routes.
Nuclear receptors (NRs) represent intracellular proteins that function as a signaling network of transcriptional factors to control genes in response to a variety of environmental, dietary, and hormonal stimulations or serve as orphan receptors lacking a recognized ligand. They also play an essential role in normal development, metabolism, cell growth, cell division, physiology, reproduction, and homeostasis and function as biological markers for tumor subclassification and as targets for hormone therapy. NRs, including steroid hormone receptors (SHRs), have been studied as tools to examine the fundamentals of transcriptional regulation within the development of mammals and human physiology, in addition to their links to disturbances. In this regard, it is widely recognized that aberrant NR signaling is responsible for the pathological growth of hormone-dependent tumors in response to SHRs dysregulation and consequently represents a potential therapeutic candidate in a range of diseases, as in the case of prostate cancer and breast cancer. On the other hand, phytosterols are a group of plant-derived compounds that act directly as ligands for NRs and have proven their efficacy in the management of diabetes, heart diseases, and cancers. However, these plants are not suggested in cases of hormone-dependent cancer since a certain group of plants contains molecules with a chemical structure similar to that of estrogens, which are known as phytoestrogens or estrogen-like compounds, such as lignans, coumestans, and isoflavones. Therefore, it remains an open and controversial debate regarding whether consuming a phytosterol-rich diet and adopting a vegetarian lifestyle like the Mediterranean diet may increase the risk of developing steroid hormone-dependent cancers by constitutively activating SHRs and thereby leading to tumor transformation. Overall, the purpose of this review is to better understand the relevant mechanistic pathways and explore epidemiological investigations in order to establish that phytosterols may contribute to the activation of NRs as cancer drivers in hormone-dependent cancers.
Grifolin is a volatile compound contained in essential oils of several medicinal plants. Several studies show that this substance has been the subject of numerous pharmacological investigations, which have yielded interesting results. Grifolin demonstrated beneficial effects for health via its multiple pharmacological activities. It has anti-microbial properties against bacteria, fungi, and parasites. In addition, grifolin exhibited remarkable anti-cancer effects on different human cancer cells. The anticancer action of this molecule is related to its ability to act at cellular and molecular levels on different checkpoints controlling the signaling pathways of human cancer cell lines. Grifolin can induce apoptosis, cell cycle arrest, autophagy, and senescence in these cells. Despite its major pharmacological properties, grifolin has only been investigated in vitro and in vivo. Therefore, further investigations concerning pharmacodynamic and pharmacokinetic tests are required for any possible pharmaceutical application of this substance. Moreover, toxicological tests and other investigations involving humans as a study model are required to validate the safety and clinical applications of grifolin.
Until recently, the main pharmaceuticals used to control cholesterol and prevent cardiovascular disease (CVD) were statin-related drugs, known for their historical side effects. Therefore, there is growing interest in exploring alternatives, such as nutritional and dietary components, that could play a central role in CVD prevention. This review aims to provide a comprehensive understanding of how natural phytosterols found in various diets combat CVDs. We begin with a description of the overall approach, then we explore in detail the different direct and indirect mechanisms that contribute to reducing cardiovascular incidents. Phytosterols, including stigmasterol, β-sitosterol, ergosterol, and fucosterol, emerge as promising molecules within nutritional systems for protection against CVDs due to their beneficial effects at different levels through direct or indirect cellular, subcellular, and molecular mechanisms. Specifically, the mentioned phytosterols exhibit the ability to diminish the generation of various radicals, including hydroperoxides and hydrogen peroxide. They also promote the activation of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione, while inhibiting lipid peroxidation through the activation of Nrf2 and Nrf2/heme oxygenase-1 (HO-1) signaling pathways. Additionally, they demonstrate a significant inhibitory capacity in the generation of pro-inflammatory cytokines, thus playing a crucial role in regulating the inflammatory/immune response by inhibiting the expression of proteins involved in cellular signaling pathways such as JAK3/STAT3 and NF-κB. Moreover, phytosterols play a key role in reducing cholesterol absorption and improving the lipid profile. These compounds can be used as dietary supplements or included in specific diets to aid control cholesterol levels, particularly in individuals suffering from hypercholesterolemia.
Diabetes is a complex disease that affects a large percentage of the world's population, and it is associated with several risk factors. Self-management poses a significant challenge, but natural sources have shown great potential in providing effective glucose reducing solutions. Flavonoids, a class of bioactive substances found in different natural sources including medicinal plants, have emerged as promising candidates in this regard. Indeed, several flavonoids, including apigenin, arbutin, catechins, and cyanidin, have demonstrated remarkable anti-diabetic properties. The clinical effectiveness of these flavonoids is linked to their potential to decrease blood glucose concentration and increase insulin concentration. Thus, the regulation of certain metabolic pathways such as glycolysis and neoglycogenesis has also been demonstrated. In vitro and in vivo investigations revealed different mechanisms of action related to flavonoid compounds at subcellular, cellular, and molecular levels. The main actions reside in the activation of glycolytic signaling pathways and the inhibition of signaling that promotes glucose synthesis and storage. In this review, we highlight the clinical efficiency of natural flavonoids as well as the molecular mechanisms underlying this effectiveness.
The Food and Drug Administration (FDA) has approved vorinostat, also called Zolinza®, for its effectiveness in fighting cancer. This drug is a suberoyl-anilide hydroxamic acid belonging to the class of histone deacetylase inhibitors (HDACis). Its HDAC inhibitory potential allows it to accumulate acetylated histones. This, in turn, can restore normal gene expression in cancer cells and activate multiple signaling pathways. Experiments have proven that vorinostat induces histone acetylation and cytotoxicity in many cancer cell lines, increases the level of p21 cell cycle proteins, and enhances pro-apoptotic factors while decreasing anti-apoptotic factors. Additionally, it regulates the immune response by up-regulating programmed death-ligand 1 (PD-L1) and interferon gamma receptor 1 (IFN-γR1) expression, and can impact proteasome and/or aggresome degradation, endoplasmic reticulum function, cell cycle arrest, apoptosis, tumor microenvironment remodeling, and angiogenesis inhibition. In this study, we sought to elucidate the precise molecular mechanism by which Vorinostat inhibits HDACs. A deeper understanding of these mechanisms could improve our understanding of cancer cell abnormalities and provide new therapeutic possibilities for cancer treatment.
The mammalian target of rapamycin (mTOR) is a highly conserved serine/threonine-protein kinase, which regulates many biological processes related to metabolism, cancer, immune function, and aging. It is an essential protein kinase that belongs to the phosphoinositide-3-kinase (PI3K) family and has two known signaling complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Even though mTOR signaling plays a critical role in promoting mitochondria-related protein synthesis, suppressing the catabolic process of autophagy, contributing to lipid metabolism, engaging in ribosome formation, and acting as a critical regulator of mRNA translation, it remains one of the significant signaling systems involved in the tumor process, particularly in apoptosis, cell cycle, and cancer cell proliferation. Therefore, the mTOR signaling system could be suggested as a cancer biomarker, and its targeting is important in anti-tumor therapy research. Indeed, its dysregulation is involved in different types of cancers such as colon, neck, cervical, head, lung, breast, reproductive, and bone cancers, as well as nasopharyngeal carcinoma. Moreover, recent investigations showed that targeting mTOR could be considered as cancer therapy. Accordingly, this review presents an overview of recent developments associated with the mTOR signaling pathway and its molecular involvement in various human cancer types. It also summarizes the research progress of different mTOR inhibitors, including natural and synthetised compounds and their main mechanisms, as well as the rational combinations with immunotherapies.
The field of nutrigenomics studies the interaction between nutrition and genetics, and how certain dietary patterns can impact gene expression and overall health. The Mediterranean diet (MedDiet), characterized by a high intake of fruits, vegetables, whole grains, and healthy fats, has been linked to better cardiovascular health (CVH) outcomes. This review summarizes the current state of research on the effects of nutrigenomics and MedDiet on cardiovascular health. Results suggest that MedDiet, through its impact on gene expression, can positively influence CVH markers such as blood pressure, lipid profile, and inflammation. However, more research is needed to fully understand the complex interactions between genetics, nutrition, and CVH, and to determine the optimal dietary patterns for individualized care. The aim of this scientific review is to evaluate the current evidence on the effects of nutrigenomics and MedDiet on cardiovascular health. The review summarizes the available studies that have investigated the relationship between nutrition, genetics, and cardiovascular health, and explores the mechanisms by which certain dietary patterns can impact CVH outcomes. The review focuses on the effects of MedDiet, a dietary pattern that is rich in whole foods and healthy fats, and its potential to positively influence CVH through its impact on gene expression. The review highlights the limitations of current research and the need for further studies to fully understand the complex interplay between nutrition, genetics, and cardiovascular health.
Cynaroside is a flavonoid, isolated from several species belonging to the Apiaceae, Poaceae, Lamiaceae, Solanaceae, Zingiberaceae, Compositae and other families and it can be extracted from seeds, roots, stems, leaves, barks, flowers, fruits, aerial parts, and the whole plant of these species. This paper discloses the current state of knowledge on the biological/pharmacological effects and mode of action to better understand the numerous health benefits of cynaroside. Several research works revealed that cynaroside could have beneficial effects on various human pathologies. Indeed, this flavonoid exerts antibacterial, antifungal, antileishmanial, antioxidant, hepatoprotective, antidiabetic, anti-inflammatory, and anticancer effects. Additionally, cynaroside exhibits its anticancer effects by blocking MET/AKT/mTOR axis by decreasing the phosphorylation level of AKT, mTOR, and P70S6K. For antibacterial activity, cynaroside reduces biofilm development of Pseudomonas aeruginosa and Staphylococcus aureus. Moreover, the incidence of mutations leading to ciprofloxacin resistance in Salmonella typhimurium was reduced after the treatment with cynaroside. In addition, cynaroside inhibited the production of reactive oxygen species (ROS), which reduced the damage to mitochondrial membrane potential caused by hydrogen peroxide (H2O2). It also enhanced the expression of the anti-apoptotic protein Bcl-2 and lowered that of the pro-apoptotic protein Bax. Cynaroside abrogated the up-regulation of c-Jun N-terminal kinase (JNK) and p53 protein expression triggered by H2O2. All these findings suggest that cynaroside could be used to prevent certain human diseases.
Lavandula stoechas, a Mediterranean plant, renowned in traditional medicine for its health benefits, is also arousing strong interest associated with its essential oils (EOs) with promising therapeutic properties. The aim of this study was to analyze the chemical composition of the plant, as well as to study its major activities, including antioxidant, anti-diabetic, dermatoprotective, anti-inflammatory, and antibacterial effects, focusing on its major molecules. Using the GC-MS method, the main compounds identified in L. stoechas EO (LSEO) were fenchone (31.81 %) and camphor (29.60 %), followed by terpineol (13.14 %) and menthone (8.96 %). To assess their antioxidant activity, three in vitro methods were used (DPPH, FRAP, and ABTS). The results revealed that LSEO exhibited the best antiradical property (54 ± 62 μg/mL) according to the DPPH test, while fenchone demonstrated the highest antioxidant capacity (87 ± 92 μg/mL) in the FRAP test, and camphor displayed the highest antioxidant capacity (96 ± 32 μg/mL) in the ABTS test. However, these results were lower than those obtained by Trolox used as a reference. In addition, study also explored the anti-diabetic potential of LSEO and its major compounds by evaluating their inhibitory activity towards two digestive enzymes, α-glucosidase and α-amylase. Camphor (76.92 ± 2.43 μg/mL) and fenchone (69.03 ± 2.31 μg/mL) exhibited the best inhibitory activities for α-amylase and α-glucosidase assays, respectively. Interestingly, all elements of the study exerted activities superior to those of acarbose, regardless of the test performed. In contrast, the evaluation of the dermatoprotective potential was carried out in vitro by targeting two enzymes involved in cutaneous processes, tyrosinase and elastase. In this light, fenchone (53.14 ± 3.06 μg/mL) and camphor (48.39 ± 1.92 μg/mL) were the most active against tyrosinase and elastase, respectively. It should be noted that the effect of both molecules, as well as that of LSEO, ranged between 53.14 ± 3.06 and 97.45 ± 5.22 μg/mL, which was significantly lower than the standard, quercetin (IC50 of 246.90 ± 2 0.54 μg/mL) against tyrosinase. Furthermore, the anti-inflammatory potential of these elements has been studied by evaluating their ability to inhibit lipooxygenase (LOX), a class of enzymes involved in the inflammatory process in the human body. As a result, the LSEO demonstrated a remarkable effect with an IC50 of 6.34 ± 1.29 μg/mL, which was almost comparable to the standard, quercetin (IC50 = 3.93 ± 0.45 μg/mL). Concerning the antibacterial potential, we carried out a quantitative analysis of the various products tested, revealing a bactericidal activity of the LSEO against the strain L. monocytogenes ATCC 13932 at a minimum effective concentration (MIC = CMB = 0.25). Overall, LSEOs offer significant potential as a source of natural antioxidants, and antidiabetic and anti-inflammatory agents, as well as dermatoprotective and antibacterial compounds. Its major molecules, fenchone and camphor, showed promising activity in these areas of study, making it a valuable candidate for future research and development in the field of natural medicine.
The regulation of gene expression is fundamental to health and life and is essentially carried out at the promoter region of the DNA of each gene. Depending on the molecular context, this region may be accessible or non-accessible (possibility of integration of RNA polymerase or not at this region). Among enzymes that control this process, DNA methyltransferase enzymes (DNMTs), are responsible for DNA demethylation at the CpG islands, particularly at the promoter regions, to regulate transcription. The aberrant activity of these enzymes, i.e. their abnormal expression or activity, can result in the repression or overactivation of gene expression. Consequently, this can generate cellular dysregulation leading to instability and tumor development. Several reports highlighted the involvement of DNMTs in human cancers. The inhibition or activation of DNMTs is a promising therapeutic approach in many human cancers. In the present work, we provide a comprehensive and critical summary of natural bioactive molecules as primary inhibitors of DNMTs in human cancers. The active compounds hold the potential to be developed as anti-cancer epidrugs targeting DNMTs.
Oxidative stress results from a persistent imbalance in oxidation levels that promotes oxidants, playing a crucial role in the early and sustained phases of DNA damage and genomic and epigenetic instability, both of which are intricately linked to the development of tumors. The molecular pathways contributing to carcinogenesis in this context, particularly those related to double-strand and single-strand breaks in DNA, serve as indicators of DNA damage due to oxidation in cancer cases, as well as factors contributing to epigenetic instability through ectopic expressions. Oxidative stress has been considered a therapeutic target for many years, and an increasing number of studies have highlighted the promising effectiveness of natural products in cancer treatment. In this regard, we present significant research on the therapeutic targeting of oxidative stress using natural molecules and underscore the essential role of oxidative stress in cancer. The consequences of stress, especially epigenetic instability, also offer significant therapeutic prospects. In this context, the use of natural epi-drugs capable of modulating and reorganizing the epigenetic network is beginning to emerge remarkably. In this review, we emphasize the close connections between oxidative stress, epigenetic instability, and tumor transformation, while highlighting the role of natural substances as antioxidants and epi-drugs in the anti-tumoral context.
Colorectal cancer (CRC) is one of the most significant forms of human cancer. It is characterized by its heterogeneity because several molecular factors are involved in contiguity and can link it to others without having a linear correlation. Among the factors influencing tumor transformation in CRC, transforming growth factor-beta (TGF-β) plays a key promoter role. This factor is associated with human colorectal tumors with a very high prognosis: it increases the survival, invasion, and metastasis of CRC cells, thus functioning as an oncogene. The inhibition of this factor can constitute a major therapeutic route for CRC treatment. Various chemical drugs including synthetic molecules and biotherapies have been developed as TGF-β inhibitors. Moreover, the scientific community has recently shown a major interest in screening natural drugs inhibiting TGF-β in CRC. In this context, we carried out this review article using computerized databases, such as PubMed, Google Scholar, Springer Link, Science Direct, Cochrane Library, Embase, Web of Science, and Scopus, to highlight the molecular mechanism of TGF-β in CRC induction and progression and current advances in the pharmacodynamic effects of natural bioactive substances targeting TGF-β in CRC.
Cyanobacteria and microalgae contain various phytochemicals, including bioactive components in the form of secondary metabolites, namely flavonoids, phenolic acids, terpenoids, and tannins, with remarkable anticancer effects. This review highlights the recent advances in bioactive compounds, with potential anticancer activity, produced by cyanobacteria and microalgae. Previous in vitro investigations showed that many of these bioactive compounds exhibit potent effects against different human cancer types, such as leukemia and breast cancers. Multiple mechanisms implicated in the antitumor effect of these compounds were elucidated, including their ability to target cellular, subcellular, and molecular checkpoints linked to cancer development and promotion. Recent findings have highlighted various mechanisms of action of bioactive compounds produced by cyanobacteria and microalgae, including induction of autophagy and apoptosis, inhibition of telomerase and protein kinases, as well as modulation of epigenetic modifications. In vivo investigations have demonstrated a potent anti-angiogenesis effect on solid tumors, as well as a reduction in tumor volume. Some of these compounds were examined in clinical investigations for certain types of cancers, making them potent candidates/scaffolds for antitumor drug development.