Therapeutic Potential of Naturally Occurring Small Molecules to Target the Wnt/β-Catenin Signaling Pathway in Colorectal Cancer

Colorectal cancer (CRC) ranks second in the number of cancer deaths worldwide, mainly due to late diagnoses, which restrict treatment in the potentially curable stages and decrease patient survival. The treatment of CRC involves surgery to remove the tumor tissue, in addition to radiotherapy and systemic chemotherapy sessions. However, almost half of patients are resistant to these treatments, especially in metastatic cases, where the 5-year survival rate is only 12%. This factor may be related to the intratumoral heterogeneity, tumor microenvironment (TME), and the presence of cancer stem cells (CSCs), which is impossible to resolve with the standard approaches currently available in clinical practice. CSCs are APC-deficient, and the search for alternative therapeutic agents such as small molecules from natural sources is a promising strategy, as these substances have several antitumor properties. Many of those interfere with the regulation of signaling pathways at the central core of CRC development, such as the Wnt/β-catenin, which plays a crucial role in the cell proliferation and stemness in the tumor. This review will discuss the use of naturally occurring small molecules inhibiting the Wnt/β-catenin pathway in experimental CRC models over the past decade, highlighting the molecular targets in the Wnt/β-catenin pathway and the mechanisms through which these molecules perform their antitumor activities.

AntiGan: An Epinutraceutical Bioproduct with Antitumor Properties in Cultured Cell Lines

Novel and effective chemotherapeutic agents are needed to improve cancer treatment. Epidrugs are currently used for cancer therapy but also exhibit toxicity. Targeting the epigenetic apparatus with bioproducts may aid cancer prevention and treatment. To determine whether the lipoprotein marine extract AntiGan shows epigenetic and antitumor effects, cultured HepG2 (hepatocellular carcinoma) and HCT116 (colorectal carcinoma) cell lines were treated with AntiGan (10, 50, 100, and to 500 µg/mL) for 24 h, 48 h, and 72 h. AntiGan (10 µg/mL) reduced cell viability after 48 h and increased Bax expression; AntiGan (10 and 50 µg/mL) increased caspase-3 immunoreactivity in HepG2 and HCT116 cells. AntiGan (10 and 50 µg/mL) attenuated COX-2 and IL-17 expression in both cell lines. AntiGan (10 µg/mL) increased 5mC levels in both cell types and reduced DNMT1 and DNMT3a expression in these cells. AntiGan (10 and 50 µg/mL) promoted DNMT3a immunoreactivity and reduced SIRT1 mRNA expression in both cell types. In HCT116 cells treated with AntiGan (10 µg/mL), SIRT1 immunoreactivity localized to nuclei and the cytoplasm; AntiGan (50 µg/mL) increased cytoplasmic SIRT1 localization in HCT116 cells. AntiGan is a novel antitumoral bioproduct with epigenetic properties (epinutraceutical) for treating liver and colorectal cancer.

A selective fluorescent probe based on citrate doped polypyrrole for dual determination of VO2+/Fe3+ in biological samples

Vanadyl sulfate has been widely utilized in the medical field due to its physiological performance like muscle improvement, insulin-mimetic activity, and antitumor properties. Herein, we have developed a facile and...

Influence of Ethanol Extracts From Pholiota Adiposa on Gut Microbiota and Their Antitumor Properties in H22 Tumor-Bearing Mice

Hepatocellular carcinoma (HCC) is a common type of cancer—prevalent worldwide—and one of the causes of cancer-related deaths. In this study, ethanol extracts from Pholiota adiposa (EPA) were used to identify possible targets for HCC treatment and their effects on intestinal microflora were analyzed. Methods: Male mice were randomly assigned to groups—the model group, cyclophosphamide (25 mg/kg/d), and EPA groups, in which the mice were categorized based on the different concentrations of each compound (100, 200, and 300 mg/kg/day). Relevant biochemical indicators were detected using ELISA, H&E staining, and TUNEL assay. Four tumor apoptosis-related proteins and genes, Caspase3, BAX, Bcl-2, and VEGF, were detected by immunohistochemical staining, western blotting, and RT-PCR. The total genomic DNA was obtained from the contents of the small intestine and colon and was sequenced. The V3+V4 regions of bacterial 16s rDNA (from 341 to 806) were amplified. Results: The tests revealed that EPA exhibited antitumor activity in vivo by promoting apoptosis and inhibiting angiogenesis. Moreover, EPA treatment could increase beneficial and decrease harmful microflorae. These results demonstrate that EPA may be a potential therapy for HCC.

Marine Bioactive Compounds as Nutraceutical and Functional Food Ingredients for Potential Oral Health

Oral diseases have received considerable attention worldwide as one of the major global public health problems. The development of oral diseases is influenced by socioeconomic, physiological, traumatic, biological, dietary and hygienic practices factors. Currently, the main prevention strategy for oral diseases is to inhibit the growth of biofilm-producing plaque bacteria. Tooth brushing is the most common method of cleaning plaque, aided by mouthwash and sugar-free chewing gum in the daily routine. As the global nutraceutical market grows, marine bioactive compounds are becoming increasingly popular among consumers for their antibacterial, anti-inflammatory and antitumor properties. However, to date, few systematic summaries and studies on the application of marine bioactive compounds in oral health exist. This review provides a comprehensive overview of different marine-sourced bioactive compounds and their health benefits in dental caries, gingivitis, periodontitis, halitosis, oral cancer, and their potential use as functional food ingredients for oral health. In addition, limitations and challenges of the application of these active ingredients are discussed and some observations on current work and future trends are presented in the conclusion section.

Cardiac Glycosides as Autophagy Modulators

Drug repositioning is one of the leading strategies in modern therapeutic research. Instead of searching for completely novel substances and demanding studies of their biological effects, much attention has been paid to the evaluation of commonly used drugs, which could be utilized for more distinct indications than they have been approved for. Since treatment approaches for cancer, one of the most extensively studied diseases, have still been very limited, great effort has been made to find or repurpose novel anticancer therapeutics. One of these are cardiac glycosides, substances commonly used to treat congestive heart failure or various arrhythmias. Recently, the antitumor properties of cardiac glycosides have been discovered and, therefore, these compounds are being considered for anticancer therapy. Their mechanism of antitumor action seems to be rather complex and not fully uncovered yet, however, autophagy has been confirmed to play a key role in this process. In this review article, we report on the up-to-date knowledge of the anticancer activity of cardiac glycosides with special attention paid to autophagy induction, the molecular mechanisms of this process, and the potential employment of this phenomenon in clinical practice.

Cascade Transformations of 1-R-Ethynyl-9,10-anthraquinones with Amidines: Expanding Access to Isoaporphinoid Alkaloids

The interaction of acetamidine and phenylamidine with peri-R-ethynyl-9,10-anthraquinones in refluxing n-butanol leads to the formation of cascade transformations products: addition/elimination/cyclization―2-R-7H-dibenzo[de,h]quinolin-7-ones and(or) 2-R-3-aroyl-7H-dibenzo[de,h]quinolin-7-ones. The anti-inflammatory and antitumor properties of the new 2-R-7H-dibenzo[de,h]quinolin-7-ones were investigated in vivo, in vitro, and in silico. The synthesized compounds exhibit high anti-inflammatory activity at dose 20 mg/kg (intraperitoneal injection) in the models of exudative (histamine-induced) and immunogenic (concanavalin A-induced) inflammation. Molecular docking data demonstrate that quinolinones can potentially intercalate into DNA similarly to the antitumor drug doxorubicin.