Enzyme Inhibitory and Anti-cancer Properties of Moringa peregrina / Propiedades inhibidoras Enzimáticas y Anticancerígenas de la Moringa peregrina

Background: Moringa peregrina is widely used in the traditional medicine of the Arabian Peninsula to treat various ailments, because it has many pharmacologically active components with several therapeutic effects. Objective: This study aimed to investigate the inhibitory effect of Moringaperegrina seed ethanolic extract (MPSE) against key enzymes involved in human pathologies, such as angiogenesis (thymidine phosphorylase), diabetes (α-glucosidase), and idiopathic intracranial hypertension (carbonic anhydrase). In addition, the anticancer properties were tested against the SH-SY5Y (human neuroblastoma). Results: MPSE extract significantly inhibited α-glucosidase, thymidine phosphorylase, and carbonic anhydrase with half-maximal inhibitory concentrations (IC50) values of 303.1 ± 1.3, 471.30 ± 0.3, and 271.30 ± 5.1 µg/mL, respectively. Furthermore, the antiproliferative effect of the MPSE was observed on the SH-SY5Y cancer cell line with IC50 values of 55.1 µg/mL. Conclusions: MPSE has interesting inhibitory capacities against key enzymes and human neuroblastoma cancer cell line.

Antecedentes: La Moringa peregrina se utiliza ampliamente en la medicina tradicional de la Península Arábiga para tratar diversas dolencias, ya que posee numerosos componentes farmacológicamente activos con varios efectos terapéuticos. Objetivo: Este estudio tenía como objetivo investigar el efecto inhibidor del extracto etanólico de semillas de Moringaperegrina (MPSE) frente a enzimas clave implicadas en patologías humanas, como la angiogénesis (timidina fosforilasa), la diabetes (α-glucosidasa) y la hipertensión intracraneal idiopática (anhidrasa carbónica). Además, se comprobaron las propiedades anticancerígenas frente al SH-SY5Y (neuroblastoma humano). Resultados: El extracto de MPSE inhibió significativamente la α-glucosidasa, la timidina fosforilasa y la anhidrasa carbónica con concentraciones inhibitorias semimáximas (IC50) de 303,1 ± 1,3, 471,30 ± 0,3 y 271,30 ± 5,1 µg/mL, respectivamente. Además, se observó el efecto antiproliferativo del MPSE en la línea celular del cáncer SH-SY5Y con valores de IC50 de 55,1 µg/mL. Conclusiones: MPSE posee interesantes capacidades inhibitorias frente a enzimas clave y línea celular de neuroblastoma canceroso humano.

A Comparative Review of Key Isothiocyanates and Their Health Benefits.

Isothiocyanates are biologically active products resulting from the hydrolysis of glucosinolates predominantly present in cruciferous vegetables belonging to the Brassicaceae family. Numerous studies have demonstrated the diverse bioactivities of various isothiocyanates, encompassing anticarcinogenic, anti-inflammatory, and antioxidative properties. Nature harbors distinct isothiocyanate precursors, glucosinolates such as glucoraphanin and gluconastrin, each characterized by unique structures, physical properties, and pharmacological potentials. This comprehensive review aims to consolidate the current understanding of Moringa isothiocyanates, mainly 4-[(α-L-rhamnosyloxy) benzyl] isothiocyanate), comparing this compound with other well-studied isothiocyanates such as sulforaphane and phenyl ethyl isothiocyanates. The focus is directed toward elucidating differences and similarities in the efficacy of these compounds as agents with anticancer, anti-inflammatory, and antioxidative properties.

An effective treatment approach of liposomally encapsulated metformin in colon cancer.

Metformin is a drug that is widely used in the treatment of type-2 diabetes and its anticarcinogenic effect has been detected in many studies since the 2000s. Metformin has a short half-life and poor biocompatibility, which limits the activity of the drug. As a solution to this situation, our study aimed to increase the anticarcinogenic effects and reduce the side effects of metformin in colon cancer by liposomal encapsulation. For this purpose, in our study, liposome production was carried out using the thin film hydration method. The amount of metformin loaded in liposomes was determined by a standard absorbance curve at 237 nm. Size distributions and membrane zeta potentials of the liposomes were evaluated with Malvern Zetasizer ZS90. Transmission electron microscopy was performed by staining the liposomes negatively with uranyl acetate. Cultured HT-29 cells were treated with liposomal metformin or free metformin at concentrations of 0, 10, 20, and 40 mM for 24 and 48 h. At the end of the treatment period, cell viability was evaluated by CellTiter-Glo luminescent cell viability test. The anticarcinogenic effects of liposomal and free metformin on HT-29 cells were compared. As a result, liposome encapsulated metformin treatment for 24 h was more effective on HT-29 cells at 20- and 40-mM concentrations causing significantly greater decrease in the IC-50 dose compared to the free metformin. The result suggests that liposomal encapsulated metformin may offer a promising approach to increase the efficacy of the drug in the treatment of colon cancer.

The Garlic Compound, Diallyl Trisulfide, Attenuates Benzo[a]Pyrene-Induced Precancerous Effect through Its Antioxidant Effect, AhR Inhibition, and Increased DNA Repair in Human Breast Epithelial Cells.

Exposure to B[a]P, the most characterized polycyclic aromatic hydrocarbon, significantly increases breast cancer risk. Our lab has previously reported that diallyl trisulfide (DATS), a garlic organosulfur compound (OSC) with chemopreventive and cell cycle arrest properties, reduces lipid peroxides and DNA damage in normal breast epithelial (MCF-10A) cells. In this study, we evaluated the ability of DATS to block the B[a]P-induced initiation of carcinogenesis in MCF-10A cells by examining changes in proliferation, clonogenic formation, reactive oxygen species (ROS) formation, 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, and protein expression of ARNT/HIF-1ß, CYP1A1, and DNA POLß. The study results indicate that B[a]P increased proliferation, clonogenic formation, ROS formation, and 8-OHdG levels, as well as increasing the protein expression of ARNT/HIF-1ß and CYP1A1 compared to the control. Conversely, DATS/B[a]P co-treatment (CoTx) inhibited cell proliferation, clonogenic formation, ROS formation, and 8-OHdG levels compared to B[a]P alone. Treatment with DATS significantly inhibited (p < 0.0001) AhR expression, implicated in the development and progression of breast cancer. The CoTx also attenuated all the above-mentioned B[a]P-induced changes in protein expression. At the same time, it increased DNA POLß protein expression, which indicates increased DNA repair, thus causing a chemopreventive effect. These results provide evidence for the chemopreventive effects of DATS in breast cancer prevention.

Fatty acid modification of casein bioactive peptides nano-assemblies, synthesis, characterization and anticarcinogenic effect.

In this study, the nano-assemblies of bovine casein hydrolyzed peptides (HP) modified by fatty acids with various alkyl chain lengths (C8, C10, C12 and C14) were synthesized. The physicochemical properties of HP-C8-HP-C14 nano-assemblies were characterized using spectra, laser particle size analyzer, contact angle meter, scanning electron microscope (SEM) and cryo-transmission electron microscope (Cryo-TEM). HP-C8 and HP-C10 self-assembled into a hollow cube cage with an average size of ~500 nm, and the assembly of HP-C12 showed a flower-shaped morphology with more dispersed behavior, and droplet size was observed as ~20 nm. The in vitro cytotoxicity against human breast cancer cells MCF-7 was tested using CCK-8 assay and flow cytometry analysis. HP-C12 showed the highest cytotoxicity for MCF-7 cells with an inhibition rate of 66.03 % ± 0.35 % with an IC50 value of 7.4 µM among HP-Cn. HP-C8, HP-C10 and HP-C12 significantly affected on the migration, invasion and apoptosis of MCF-7 cells. The apoptosis mechanism may depend on the upregulation of anti-apoptotic protein Bcl-2 as well as pro-apoptotic proteins Bax and caspase-8. The dead MCF-7 cells were analyzed with UHPLC-MS/MS using untargeted metabolomics, revealing key metabolic pathways.

Brassica-derived isothiocyanates as anticancer therapeutic agents and their nanodelivery.

The isothiocyanates (ITCs) derived from the precursor glucosinolate molecules present in Brassica vegetables are bioactive organo-sulfur compounds with numerous pharmacologically important properties such as antioxidant, antiinflammatory, antimicrobial, and anticancer. Over the years, ITCs have been the focus of several research investigations associated with cancer treatment. Due to their potent chemo-preventive action, ITCs have been considered to be promising therapeutics for cancer therapy in place of the already existing conventional anticancer drugs. However, their wide spread use at the clinical stage is greatly restricted due to several factors such as low solubility in an aqueous medium, low bioavailability, low stability, and hormetic effect. To overcome these hindrances, nanotechnology can be exploited to develop nano-scale delivery systems that have the potential to enhance stability, and bioavailability and minimize the hermetic effect of ITCs.

Chemopreventive Effects of Polysaccharides and Flavonoids from Okra Flowers in Azomethane/Dextran Sulfate Sodium-Induced Murine Colitis-Associated Cancer.

Okra flowers are a good source of polysaccharides and flavonoids, with biological activities of anti-inflammatory action and modulation of the gut microbiota. Previously, we reported that flavonoid-rich extracts from okra flowers (AFE) presented effective anti-colorectal cancer (CRC) activity in CRC cells as well as xenograft models, but their role in colitis-associated cancer (CAC) is unidentified. In this study, we aimed to evaluate the effects of AFE and APE (polysaccharides extracted from okra flowers) on the CAC symptoms of azoxymethane (AOM)/dextran sodium sulfate (DSS)-intervened mice. The results showed that APE and AFE exert potent efficacy in inhibiting colitis and colorectal tumorigenesis stimulated by AOM/DSS, characterized by decreased colonic shortening, DAI score, and tumor numbers. Compared with the control group, APE/AFE alleviated the microbiota dysbiosis driven by AOM/DSS. In addition, AFE elicited its anticancer activity through regulation of NFκB/IL-6/Stat3, JAK2/Stat3, MAPKs, PI3K/AKT, and Wnt/ß-catenin signal transductions in AOM/DSS mice, which was consistent with a vitro model of CT26 cells, while APE treatment exhibited anticancer activity through regulation of Nrf2/IL-6, MAPKs, PI3K/AKT, and Wnt/ß-catenin signal transductions in the AOM/DSS mouse model. Collectively, our studies revealed, for the first time, that flavonoids and polysaccharides from okra flowers possess the ability to attenuate colitis and colorectal tumorigenesis, with them having great potential to become promising candidates against CRC.

Potential chemopreventive effects of Broccoli extract supplementation against 7, 12 dimethyl Benz(a)anthracene (DMBA) -induced toxicity in female rats.

Dietary components have recently received rapidly expanding attention for their potential to halt or reverse the development of many oxidative stress-mediated diseases after exposure to environmental toxicants. 7, 12 dimethylbenz(a)anthracene (DMBA) is one of the most common environmental pollutants. The present study aimed to evaluate the chemo-preventive effects of broccoli as a nutritional component against DMBA intoxication in rats. A daily dose of aqueous (1 ml/rat) and methanolic (150 mg/kg) broccoli extracts, respectively, was given to 50-day-old female rats for 26 successive weeks after carcinogen intoxication with a single dose of 20 mg/ml of DMBA. DMBA intoxication resulted in a redox imbalance (a decreased GSH level and an increased MDA level) and increased DNA fragmentation in the liver, kidney, and brain. Besides, it affected the level of expression of the bcl2 gene in the liver, kidney, and brain tissue but didn't affect cfos gene expression accompanied by histopathological changes. The aqueous and methanolic broccoli extract supplements ameliorated the adverse effects by increasing the level of GSH, decreasing the MDA level, and reducing DNA fragmentation. Besides, broccoli extracts decreased the expression of bcl2 in the liver and brain and up-regulated bcl2 expression in the kidney, accompanied by lowering NF-κß 65 expression in the liver and brain and γ-catenin expression in the liver and kidney. In conclusion, broccoli as a dietary component had a strong chemoprotective effect against oxidative stress, DNA damage, and genotoxicity induced by DMBA intoxication in rats.

Flavonoids as promising anticancer therapeutics: Contemporary research, nanoantioxidant potential, and future scope.

Flavonoids are natural polyphenolic compounds considered safe, pleiotropic, and readily available molecules. It is widely distributed in various food products such as fruits and vegetables and beverages such as green tea, wine, and coca-based products. Many studies have reported the anticancer potential of flavonoids against different types of cancers, including solid tumors. The chemopreventive effect of flavonoids is attributed to various mechanisms, including modulation of autophagy, induction of cell cycle arrest, apoptosis, and antioxidant defense. Despite of significant anticancer activity of flavonoids, their clinical translation is limited due to their poor biopharmaceutical attributes (such as low aqueous solubility, limited permeability across the biological membranes (intestinal and blood-brain barrier), and stability issue in biological systems). A nanoparticulate system is an approach that is widely utilized to improve the biopharmaceutical performance and therapeutic efficacy of phytopharmaceuticals. The present review discusses the significant anticancer potential of promising flavonoids in different cancers and the utilization of nanoparticulate systems to improve their nanoantioxidant activity further to enhance the anticancer activity of loaded promising flavonoids. Although, various plant-derived secondary metabolites including flavonoids have been recommended for treating cancer, further vigilant research is warranted to prove their translational values.

An Update on Potential Molecular Biomarkers of Dietary Phytochemicals Targeting Lung Cancer Interception and Prevention.

Since ancient times, dietary phytochemicals are known for their medicinal properties. They are broadly classified into polyphenols, terpenoids, alkaloids, phytosterols, and organosulfur compounds. Currently, there is considerable interest in their potential health effects against various diseases, including lung cancer. Lung cancer is the leading cause of cancer deaths with an average of five-year survival rate of lung cancer patients limited to just 14%. Identifying potential early molecular biomarkers of pre-malignant lung cancer cells may provide a strong basis to develop early cancer detection and interception methods. In this review, we will discuss molecular changes, including genetic alterations, inflammation, signal transduction pathways, redox imbalance, epigenetic and proteomic signatures associated with initiation and progression of lung carcinoma. We will also highlight molecular targets of phytochemicals during lung cancer development. These targets mainly consist of cellular signaling pathways, epigenetic regulators and metabolic reprogramming. With growing interest in natural products research, translation of these compounds into new cancer prevention approaches to medical care will be urgently needed. In this context, we will also discuss the overall pharmacokinetic challenges of phytochemicals in translating to humans. Lastly, we will discuss clinical trials of phytochemicals in lung cancer patients.

Oleuropein exhibits anticarcinogen effects against gastric cancer cell lines.

BACKGROUND: Oleuropein (OLE), the main phenolic compound of the olive fruit and leaves, has many heathful effects. Gastric cancer is the most fatal malignancy in many parts of the world and it is generally related to harmful dietetic factors. The anticarcinogenic role of OLE in gastric cancer has not been studied sufficiently yet. In this study, we aimed to research the cytotoxic, genotoxic and apoptotic effects of OLE on gastric adenocancer (AGS) cells in vitro. METHODS AND RESULTS: A standard cell line derived from gastric adeno cancer (AGS) cells was employed, and its performance following a 24-hour exposure to OLE at various doses was examined. The ATP cell viability assay, 2',7'-dichlorodihydrofluorescein-diacetate assay (H2DCF-DA) and alkaline single cell gel electrophoresis assay (Comet Assay) were used to study the cytotoxicity, production of reactive oxygen species (ROS) and genotoxicity respectively. The induction of apoptosis was discovered using flow cytometry. OLE reduced AGS cells viability about 60% at maximum concentration (500 µmol/L) and also resulted in approximately 100% DNA damage and about 40% apoptosis with necrosis in AGS cells depending on the increased doses. Cell viability was also significantly decreased in relation to increased intracellular reactive oxygen species (ROS) levels (p < 0.05 - 0.001). CONCLUSIONS: Oleuropein has shown significant anticarcinogen effects against gastric adenocancer (AGS) cells in vitro. Oleuropein, a nutrient rich in olive and olive oil, seems to be both protective and therapeutic against gastric cancer and may be a new chemotherapeutic agent in the future.

In vitro anti-carcinogenic effect of andarine as a selective androgen receptor modulator on MIA-PaCa-2 cells by decreased proliferation and cell-cycle arrest at G0/G1 phase.

Pancreatic cancer (PC) continues to be devastating due to its highly malignant nature and poor prognosis. The limited benefits of the chemotherapeutic drugs and increasing resistance pose a critical challenge to overcome and warrant investigations for new therapeutic agents. Several preclinical and clinical studies have suggested a possible role of the androgen receptor (AR) signaling pathway in PC development and progression. Nevertheless, the studies are limited and inconclusive in explaining the molecular link between AR signaling and PC. Selective androgen receptor modulators (SARMs) are small molecule drugs with high affinity for the androgen receptor. SARMs elicit selective anabolic activities while abrogating undesired androgenic side effects. There is no study focusing on the utility of SARMs as inhibitors of PC. Here, we report the first study evaluating the possible anti-carcinogenic influences of andarine, a member of the SARMs, on PC. The data we presented here has illustrated that andarine repressed PC cell growth and proliferation via cell cycle arrest at G0/G1 phase. Gene expression analysis revealed that it downregulates CDKN1A expression level accordingly. Furthermore, we established that the anti-carcinogenic activity of andarine is not mediated by the PI3K/AKT/mTOR signaling pathway, a crucial regulator of cell survival. Our findings suggest that andarine might be considered as a prospective drug for PC.

Carotenoids for lung cancer chemoprevention and chemotherapy: Promises and controversies.

BACKGROUND: Lung cancer is one of the leading causes of malignancy in the world. Several therapeutical and chemopreventive approaches have been practised to mitigate the disease. The use of phytopigments including carotenoids is a well-known approach. However, some of the prominent clinical trials interrogated the efficacy of carotenoids in lung cancer prevention. METHODS: A elaborate literature survey have been performed investigating in vitro, in vivo, and clinical studies reported on the administration of carotenoids for chemoprevention and chemotherapy. RESULTS: Tobacco consumption, genetic factors, dietary patterns, occupational carcinogens, lung diseases, infection, and sex disparities are some of the prominent factors leading to lung cancer. Significant evidence has been found underlining the efficiency of carotenoids in alleviating cancer. In vitro studies have proven that carotenoids act through PI3K/ AKT/mTOR, ERK-MAPK pathways and induce apoptosis through PPAR, IFNs, RAR, which are p53 intermediators in lung cancer signaling. Animal models and cell lines studies showed promising results, while the outcomes of clinical trials are contradictory and require further verification. CONCLUSION: The carotenoids exert chemotherapeutic and chemopreventive effects on lung tumors which has been evidenced in numerous investigations. However, further analyses are necessary to the answer the uncertainties raised by several clinical trials.

The anticarcinogenic effect of eugenol on lung cancer induced by diethylnitrosamine/2-acetylaminofluorene in Wistar rats: insight on the mechanisms of action.

This study was designed to assess the ameliorative effects of eugenol and to propose the possible mechanisms of action of eugenol in diethylnitrosamine (DENA)/acetylaminofluorene (AAF)-caused lung cancer in Wistar rats. To induce lung cancer, DENA at a dose of 150 mg/kg body weight (b.wt) for 2 weeks were intraperitoneally injected once each week and AAF was administered orally at a dose of 20 mg/kg b.wt. four times each week for the next 3 weeks. DENA/AAF-administered rats were orally supplemented with eugenol at a dose of 20 mg/kg b.wt administered once a day until 17 weeks starting from the 1st week of DENA administration. Lung histological lesions, including sheets of tumor cells, micropapillary adenocarcinoma, and apoptotic cells, resulting from the DENA/AAF dosage, were ameliorated by eugenol treatment. However, a significant drop in the levels of LPO in the lungs and a remarkable rise in GSH content and GPx and SOD activities were observed in DENA/AAF-administered rats treated with eugenol compared with those in DENA/AAF-administered controls. Moreover, in DENA/AAF-administered rats, eugenol supplementation significantly reduced TNF-α and IL-1ß levels and mRNA expression levels of NF-κB, NF-κB p65, and MCP-1 but significantly elevated the level of Nrf2. Furthermore, the DENA/AAF-administered rats treated with eugenol exhibited a significant downregulation of Bcl-2 expression levels in addition to a significant upregulation in P53 and Bax expression levels. Otherwise, the administration of DENA/AAF elevated the protein expression level of Ki-67, and this elevation was reversed by eugenol treatment. In conclusion, eugenol has effective antioxidant, anti-inflammatory, proapoptotic, and antiproliferative properties against lung cancer.

The Role of Phytochemicals in Cancer Prevention: A Review with Emphasis on Baicalein, Fisetin, and Biochanin A.

Cancer is a disease in which repeated rounds of mutations cause uncontrolled growth of cells, which prospers at the expense of their neighbor cells and then eventually leads to the destruction of the whole cellular community. Chemopreventive drugs either prevent DNA damage, which results in malignancy, or they stop or reverse the division of premalignant cells with DNA damage, which inhibits the growth of cancer. There is an obvious need for an alternate strategy given the ongoing rise in cancer incidence, the ineffectiveness of traditional chemotherapies to control cancer, and the excessive toxicity of chemotherapies. From antiquity to date, the saga of the usage of plants as medicine has been the mainstay among people worldwide. In recent years, extensive studies have been conducted on medicinal plants, spices, and nutraceuticals, as these have gained much popularity in reducing the risk of several cancer types in humans. Extensive studies on cell culture systems and animal models have demonstrated that various medicinal plants and nutraceuticals from various natural resources and their products, such as major polyphenolic constituents, flavones, flavonoids, antioxidants, etc, provide considerable protection against many cancer types. As shown in the literatures, the major aim of studies conducted is to develop preventive/therapeutic agents which can induce apoptosis in cancer cells without affecting normal cells. Projects are going on worldwide to find better ways to eradicate the disease. The study of phytomedicines has shed new light on this topic as research to date has proven that they have antiproliferative and apoptotic capabilities that will aid in the development of novel cancer prevention options. Dietary substances, such as Baicalein, Fisetin, and Biochanin A have shown that they have an inhibitory effect on cancer cells, suggesting that they may work as chemopreventive agents. This review discusses the chemopreventive and anticancer mechanisms of such reported natural compounds.

Insights into Pharmacological Potential of Apigenin through Various Pathways on a Nanoplatform in Multitude of Diseases.

Apigenin is a natural polyphenolic compound widely distributed as a glycoside in fruits and vegetables. Apigenin belongs to BCS class II with low solubility, which leads to poor absorption and bioavailability. It is mostly absorbed from the small intestine and extensively metabolized through glucuronidation and sulfation processes. Apigenin is known for its antioxidant and anti-inflammatory properties. It is also used as a chemopreventive drug in the management of various cancers. Pharmacological effects of apigenin have a wide range, from neuroprotective to treating renal disorders. Apigenin is non-toxic in nature and acts through various pathways (JAK/STAT, Wnt/ß-catenin, MAPK/ERK, PI3K/Akt, and NF-κB) to exert its therapeutic efficacy. Numerous formulations have been researched to enhance the bioavailability and pharmacological effects of apigenin. Combinatorial therapies are also researched to minimize the side-effects of chemotherapeutic drugs. The review presents pharmacokinetic and pharmacodynamic aspects of apigenin. Apigenin is safe for the treatment and management of numerous diseases. It can be easily incorporated into nanoformulation alone or in combination with other active ingredients to widen the therapeutic window. This review intends to help in drug optimization and therapeutic efficacy maximization for future studies.

Evaluation of the Anti-Carcinogenic Effect of Centella Asiatica on Oral Cancer Cell Line: In vitro Study.

OBJECTIVE: To evaluate the anti-carcinogenic effect of Centella Asiatica on to evaluate the  Anti-Carcinogenic Effect of Centella Asiatica on Oral Cancer Cell Line oral cancer cell line. MATERIALS AND METHODS:  Oral Cancer cell line and normal oral keratinocyte cell line were procured.Centella asiatica extract was prepared. The cells were then subjected to the test herbal specimens -Centella asiatica extract in succeeding concentrations of 25 µg/ml, 50 µg/ml, 100 µg/ml at time intervals of 24,48 and 72 hours. Cisplatin (2 µg/ml, 4 µg/ml, 6 µg/ml, 8 µg/ml) was used as a positive control. This experiment was done in triplets. RESULTS: The study revealed that the p values were less than 0.05 at concentration 12.5µg/ml, 25µg/ml, 50 µg/ml,100 µg/ml and time period of 24hrs,48hrs,72hrs, thus implying that at these concentrations and time period, the obtained data were statistically significant, thus indicating that there is a statistically significantly decreases in the viable cells as the concentration of the drug as a time period increases The results reveals that  centella asiatica possess potential effect of anti-carcinogenic, effect when compared to positive control (Cisplatin). CONCLUSION: The current study reveals that Centella asiatica has an potential anti-carcinogenic effect on oral cancer cell line. So this can be used to treat oral cancer with minimal crippling as compared with allopathic drugs.

Endoscopic and chemopreventive management of familial adenomatous polyposis syndrome.

Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome predisposing affected individuals to gastrointestinal (GI) cancers through a high burden of polyposis. Colorectal cancer rates reach 100% by the age of 45, making early colectomy a mainstay of treatment. While most patients undergo colectomy at an early age, ongoing screening and surveillance of the upper gastrointestinal tract and rectal pouch must continue throughout adulthood. Endoscopic therapy of gastric, duodenal, ampullary and rectal pouch polyps is critical to reduce morbidity and cancer related mortality. Management of these lesions is not uniform, and is dependent on their location, size, histology, and risk of malignant potential. Medical therapies targeting pathways that reduce the malignant progression of pre-cancerous lesions have been studied for many years. While studies on the use of aspirin and non-steroidal anti-inflammatories (NSAIDs) in chemoprevention have shown encouraging results in Lynch syndrome and primary colorectal cancer, the potential benefits of these medications have not been duplicated in FAP cohorts. While data remains limited on chemoprevention in FAP, a number of randomized trials are currently underway examining targeted therapies with the potential to slow the progression of the disease. This review aims to provide an in-depth review of the literature on current endoscopic options and chemopreventive therapies targeting FAP. While the endoscopic management has robust data for its use, chemoprevention in FAP is still in its infancy. The complementary use of chemopreventive agents and endoscopic therapy for FAP patients is quickly becoming a growing and exciting area of research.

Chemical characterization of Brazilian savannah Byrsonima species (muricis) and their impact on genomic instability and chemopreventive effects.

The identification of new drugs with few or no adverse effects is of great interest worldwide. In cancer therapy, natural products have been used as chemopreventive and chemotherapeutic agents. Plants from the Brazilian savannah belonging to the Byrsonima genus are popularly known as muricis and have attracted much attention due to their various pharmacological activities. However, there are currently no data on these plants concerning their use as chemopreventive or chemotherapeutic agents in human cell lines. The present study assessed the potential of B. correifolia, B. verbascifolia, B. crassifolia, and B. intermedia extracts as natural alternatives in the prevention and/or treatment of cancer. The chemical constituents present in each extract were analyzed by electrospray ionization-mass spectrometry (ESI-MSN). The mutagenic/antimutagenic (micronucleus assay), genotoxic/antigenotoxic (comet assay), apoptotic/necrotic (acridine orange/ethidium bromide uptake), and oxidative/antioxidative (CM-H2DCFDA) effects of the extracts and their influence on gene expression (RTqPCR) were investigated in nonmetabolizing gastric (MNP01) and metabolizing hepatocarcinoma (HepG2) epithelial cells to evaluate the effects of metabolism on the biological activities of the extracts. The genotoxicity, mutagenicity, and apoptotic effects observed in HepG2 cells with B. correifolia and B. verbascifolia extracts are probably associated with the presence of proanthocyanidins and amentoflavone. In MNP01 cells, none of the four extracts showed mutagenic effects. B. crassifolia and B. intermedia extracts exhibited strong antimutagenicity and enhanced detoxification in HepG2 cells and antioxidant capacities in both types of cells, possibly due to the presence of gallic and quinic acids, which possess chemopreventive properties. This study identifies for the first time B. correifolia and B. verbascifolia extracts as potential agents against hepatocarcinoma and B. crassifolia and B. intermedia extracts as putative chemopreventive agents.

Substances of Natural Origin in Medicine: Plants vs. Cancer.

Continuous monitoring of the population's health is the main method of learning about disease prevalence. National and international data draw attention to the persistently high rates of cancer incidence. This necessitates the intensification of efforts aimed at developing new, more effective chemotherapeutic and chemopreventive drugs. Plants represent an invaluable source of natural substances with versatile medicinal properties. Multidirectional activities exhibited by natural substances and their ability to modulate key signaling pathways, mainly related to cancer cell death, make these substances an important research direction. This review summarizes the information regarding plant-derived chemotherapeutic drugs, including their mechanisms of action, with a special focus on selected anti-cancer drugs (paclitaxel, irinotecan) approved in clinical practice. It also presents promising plant-based drug candidates currently being tested in clinical and preclinical trials (betulinic acid, resveratrol, and roburic acid).