Modulatory Properties of Aloe secundiflora's Methanolic Extracts on Targeted Genes in Colorectal Cancer Management.

Colon tumors have a very complicated and poorly understood pathogenesis. Plant-based organic compounds might provide a novel source for cancer treatment with a sufficient novel mode of action. The objective of this study was to analyze and evaluate the efficacy of Aloe secundiflora's (AS) methanolic extracts on the expression of CASPS9, 5-LOX, Bcl2, Bcl-xL, and COX-2 in colorectal cancer (CRC) management. Caco-2 cell lines were used in the experimental study. In the serial exhaustive extraction (SEE) method, methanol was utilized as the extraction solvent. Upon treatment of CASPS9 with the methanolic extracts, the expression of the genes was progressively upregulated, thus, dose-dependently increasing the rate of apoptosis. On the other hand, the expressions of 5-LOX, Bcl2, and Bcl-xL were variably downregulated in a dose-dependent manner. This is a unique novel study that evaluated the effects of AS methanolic extracts in vitro on CRC cell lines using different dosage concentrations. We, therefore, recommend the utilization of AS and the application of methanol as the extraction solvent of choice for maximum modulatory benefits in CRC management. In addition, we suggest research on the specific metabolites in AS involved in the modulatory pathways that suppress the development of CRC and potential metastases.

Regulatory activities of Warbugia ugandensis ethanolic extracts on colorectal cancer-specific genome expression dose-dependently.

The evaluation of natural biomass sources is a promising strategy in accelerating the development of novel anti-cancer medications. Our study aimed to evaluate the activity of W. ugandensis ethanolic roots and stems extracts on the expression of five targeted genes (COX-2, CASPS-9, Bcl-xL, Bcl2 and 5-LOX) in colorectal cancer (CRC) cell lines (Caco-2). Plant extracts were obtained using serial exhaustive extraction and dissolved in Dimethyl sulfoxide appropriately for bioassay. Caco-2 cell lines were passaged, treated with plant extracts at varying concentrations and their RNA's isolated for evaluation. Our unique study reports on W. ugandensis as efficient natural inhibitors of CRC growth, by directly linking its phytoconstituents to; downregulation of COX-2, 5-LOX, Bcl-xL, Bcl2 and upregulation of CASPS9 genes dose-dependently. We present W. ugandensis ethanolic roots and stems extracts as promising natural inhibitors for CRC carcinogenesis and recommend in vivo and subsequent clinical trials, with substantial clinical effects postulated. We further suggest studies on identification and characterization of the specific metabolites in W. ugandensis involved in the modulatory mechanisms, resulting to inhibition of CRC growth and possible metastases.

Are chemical compounds in medical mushrooms potent against colorectal cancer carcinogenesis and antimicrobial growth?

After cardiovascular diseases, cancer is the second main cause of death globally. Mushrooms have been demonstrated to contain amalgamation with properties capable of inhibiting carcinogenesis and microbial growth, principally secondary metabolites such as quinolones, steroids, terpenes, anthraquinones, and benzoic acid derivatives among others. This study aimed to substantiate their potency concerning colon cancer carcinogenesis and antimicrobial growth. A systematic search of important literature was performed considering all the articles published until April 2022. Screening was performed by searching the BMC Springer, Elsevier, Embase, Web of Science, Ovid, and MEDLINE databases. In addition, Google Scholar was used to supplement information. Titles and abstracts that matched the established criteria were selected for full-text article scrutiny and subsequently used in the updated present review. Bioactive compounds present in medicinal mushrooms such as ascorbic acid, organic acids, flavonoids, polysaccharides, glycosides, phenols, linoleic acid, grifolin, and tocopherols among other compounds play a key role in suppressing the proliferation of cancerous cells and selectively act as antibacterial and antifungal agents. These metabolites actively scavenge oxygen free radicals, hydroxyl radicals, and nitrite radicals that would otherwise increase the risks of the growth and development of cancerous cells. Mushrooms' bioactive compounds and metabolites actively inhibit nuclear factor-kappa activation, protein kinase B processes, and ultimately the expression of Cyclooxygenases 2 in cancerous cells. Medicinal mushrooms should be considered as alternative natural chemo-preventive agents in the global fight against colon cancer and the evolution of drug-resistant pathogenic microorganisms, as they exhibit robust potency. They have not been reported to exhibit adverse harmful effects compared to synthetic chemotherapies, yet they have been reported to demonstrate significant beneficial effects.

Medicinal plants with anti-colorectal cancer bioactive compounds: Potential game-changers in colorectal cancer management.

Development and identification of molecular compounds capable of killing or inhibiting transformed cells promoting carcinogenesis without inducing toxic effects to the normal cells are of utmost significance. A systematic review was conducted in screening for important literature was extensively performed by searching the Web of Science, Ovid, BMC Springer, Elsevier, Embase, and MEDLINE databases for optimum selectivity. Google Scholar was also used to supplement information. Pharmacotherapeutic biomolecules active against colon cancer carcinogenesis in Musa acuminata and Musa balbisiana (bananas), Punica granatum L (pomegranate), Glycine max (Soybean), Brassica oleracea L var. italica Plenck (Broccoli), and Hibiscus rosa-sinesis and Hibiscus sabdariffa (hibiscus) were evaluated. Signaling pathways like phosphatidylinositol 3-kinase (PI3K), mitogen-activated protein kinase (MAPK), protein kinase B (AKT), and nuclear factor-kappa B (NFκB) correlate the mediation of COX-2 expression. Increased levels of COX-2 are correlated with the occurrence and progression of colon cancer. Natural antioxidants in herbal plants including polyphenols and carotenoids inhibit the oxidation of lipids, proteins, and nucleic acids and thereby preventing the initiation of oxidizing chain reactions. These bioactive compounds should be considered an important dietary supplement.

The Chemopreventive Effects of Polyphenols and Coffee, Based upon a DMBA Mouse Model with microRNA and mTOR Gene Expression Biomarkers.

Polyphenols are capable of decreasing cancer risk. We examined the chemopreventive effects of a green tea (Camellia sinensis) extract, polyphenol extract (a mixture of blackberry (Rubus fruticosus), blackcurrants (Ribes nigrum), and added resveratrol phytoalexin), Chinese bayberry (Myrica rubra) extract, and a coffee (Coffea arabica) extract on 7,12-dimethylbenz[a]anthracene (DMBA) carcinogen-increased miR-134, miR-132, miR-124-1, miR-9-3, and mTOR gene expressions in the liver, spleen, and kidneys of CBA/Ca mice. The elevation was quenched significantly in the organs, except for miR-132 in the liver of the Chinese bayberry extract-consuming group, and miR-132 in the kidneys of the polyphenol-fed group. In the coffee extract-consuming group, only miR-9-3 and mTOR decreased significantly in the liver; also, miR-134 decreased significantly in the spleen, and, additionally, miR-124-1 decreased significantly in the kidney. Our results are supported by literature data, particularly the DMBA generated ROS-induced inflammatory and proliferative signal transducers, such as TNF, IL1, IL6, and NF-κB; as well as oncogenes, namely RAS and MYC. The examined chemopreventive agents, besides the obvious antioxidant and anti-inflammatory effects, mainly blocked the mentioned DMBA-activated factors and the mitogen-activated protein kinase (MAPK) as well, and, at the same time, induced PTEN as well as SIRT tumor suppressor genes.

The effects of flavonoids, green tea polyphenols and coffee on DMBA induced LINE-1 DNA hypomethylation.

The intake of carcinogenic and chemopreventive compounds are important nutritional factors related to the development of malignant tumorous diseases. Repetitive long interspersed element-1 (LINE-1) DNA methylation pattern plays a key role in both carcinogenesis and chemoprevention. In our present in vivo animal model, we examined LINE-1 DNA methylation pattern as potential biomarker in the liver, spleen and kidney of mice consuming green tea (Camellia sinensis) extract (catechins 80%), a chinese bayberry (Morella rubra) extract (myricetin 80%), a flavonoid extract (with added resveratrol) and coffee (Coffee arabica) extract. In the organs examined, carcinogen 7,12-dimethylbenz(a)anthracene (DMBA)-induced hypomethylation was prevented by all test materials except chinese bayberry extract in the kidneys. Moreover, the flavonoid extract caused significant hypermethylation in the liver compared to untreated controls and to other test materials. The tested chemopreventive substances have antioxidant, anti-inflammatory properties and regulate molecular biological signaling pathways. They increase glutathione levels, induce antioxidant enzymes, which decrease free radical damage caused by DMBA, and ultimately, they are able to increase the activity of DNA methyltransferase enzymes. Furthermore, flavonoids in the liver may inhibit the procarcinogen to carcinogen activation of DMBA through the inhibition of CYP1A1 enzyme. At the same time, paradoxically, myricetin can act as a prooxidant as a result of free radical damage, which can explain that it did not prevent hypomethylation in the kidneys. Our results demonstrated that LINE-1 DNA methylation pattern is a useful potential biomarker for detecting and monitoring carcinogenic and chemopreventive effects of dietary compounds.

The effect of fenugreek on the gene expression of arachidonic acid metabolizing enzymes.

The main bioactive compounds of Trigonella foenum graecum L. (fenugreek) seeds are protodioscin, trigoneoside, diosgenin and yamogenin, which have anticarcinogenic potency through inhibition of cell proliferation and inhibition of prostaglandin synthesis. The effect of fenugreek on ALOX and COX genes was examined in AKR/J H-2(k) mice exposed to dimethylbenz[α]anthracene (DMBA), a potent carcinogen. The expression pattern of these genes was determined by detecting the mRNA expression in various tissues (the lungs, liver, spleen and the kidneys) in four groups of mice. Two groups were fed with normal and two of them with fenugreek containing nutriment. Each group divided into DMBA treated and control groups. Mice were autopsied on day 7 after DMBA treatment for mRNA isolation. Fenugreek consumption itself did not change gene expression compared with the control group. DMBA could increase the expression of ALOX12, ALOX15, ALOX5 genes mainly in all organs. Fenugreek consumption was generally protective in each organ in a different manner. DMBA treatment increased COX2 gene expression, but fenugreek was protective in all tissues examined. In COX1 gene, the fenugreek diet could suppress the expression, except for spleen, independently from carcinogen exposure. Therefore by inhibiting the arachidonic acid metabolism fenugreek may prevent tumorigenesis.

Mixtures of Uncaria and Tabebuia extracts are potentially chemopreventive in CBA/Ca mice: a long-term experiment.

A long-term experimental animal model was developed by our research group for the evaluation of potential chemopreventive effects. The inhibitory effects of agents on carcinogen (7,12-dimethylbenz[a]anthracene (DMBA) induced molecular epidemiological biomarkers, in this case the expression of key onco/suppressor genes were investigated. The expression pattern of c-myc, Ha-ras, Bcl-2, K-ras protooncogene and p53 tumour suppressor gene were studied to elucidate early carcinogenic and potential chemopreventive effects. The consumption of so-called Claw of Dragon tea (CoD™ tea) containing the bark of Uncaria guianensis, Cat's Claw (Uncaria sp. U. tomentosa) and Palmer trumpet-tree (Tabebuia sp. T. avellanedae) was able to decrease the DMBA-induced onco/suppressor gene overexpression in a short-term animal experiment. In a following study CBA/Ca mice were treated with 20 mg/kg bw DMBA intraperitoneally (i.p.) and the expression patterns of onco/suppressor genes were examined at several time intervals. According to the examined gene expression patterns in this long-term experiment the chemopreventive effect of CoD™ tea consumption could be confirmed.

The plant-derived natural compound Flavin 7 attenuates oxidative stress in cultured renal proximal tubule cells.

BACKGROUND: Cancer therapies and cancer progression can increase oxidative stress that might account for renal toxicity in cancer patients. Flavin 7 (F7) is a natural polyphenol-containing dietary supplement with potential antioxidant activity. Therefore, it might help to attenuate renal toxicity of chemotherapeutics. MATERIALS AND METHODS: Cultured mouse renal proximal tubule cells were subjected to H(2)O(2)-mediated oxidative stress. Potential antioxidant effects of F7 were assessed by measuring the production of reactive oxygen species (ROS), mitochondrial depolarization and injury (lactate dehydrogenase release as well as trypan blue exclusion) in cells that were pretreated with F7 prior to treatment with H(2)O(2). RESULTS: F7 pretreatment significantly attenuated H(2)O(2)-induced ROS production, mitochondrial depolarization and consequent injury in renal proximal tubule cells. CONCLUSION: F7 supplementation might be beneficial for cancer patients in order to prevent renal toxicity of anticancer drug- or cancer progression-related oxidative stress.