Ganoderma lucidum polysaccharides inhibit in vitro tumorigenesis, cancer stem cell properties and epithelial-mesenchymal transition in oral squamous cell carcinoma.

ETHNOPHARMACOLOGICAL RELEVANCE: The polysaccharides of the millenary mushroom Ganoderma lucidum (GL) have been shown for decades to present anti-tumor activities, but few studies evaluated its importance on cancer stem cells and EMT process. Cancer stem cells (CSC) drive the development of carcinoma and are also involved in cancer treatment failure, being a good target for treatment success. Also, the process of epithelial-mesenchymal transition (EMT) is involved in metastasis and cancer relapse. Besides that, the increasing incidence worldwide of oral squamous cell carcinoma (OSCC) became a public health issue with a high rate of metastasis and poor quality of life for patients during and after treatment. AIM OF THE STUDY: to evaluate G. lucidum polysaccharides (GLPS) in vitro effects on OSCC, focusing on hallmarks associated with tumorigenesis using the SCC-9, a squamous cells carcinoma lineage from the tongue. MATERIALS AND METHODS: SCC-9 cells were treated in vitro for 72h with different GLPS concentrations. The controls cells were maintained with culture media only and cisplatin was used as treatment control. After the treatment period, the cells were evaluated. RESULTS: GLPS treatment changed cell morphology and granularity, delayed migration, decreased colony, and impaired sphere formation, thereby leading to a non-invasive and less proliferative behavior of tumoral cells. Additionally, GLPS downregulated CSC, EMT, and drug sensitivity (ABC) markers. CONCLUSIONS: These results show that the natural product GLPS has the potential to be an important ally for tongue squamous cell carcinoma treatment, bringing the millenary compound to modern therapy, providing a basis for future studies and the improvement of life quality for OSCC patients.

Role of diet and gut microbiota on colorectal cancer immunomodulation.

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers, and it is characterized by genetic and epigenetic alterations, as well as by inflammatory cell infiltration among malignant and stromal cells. However, this dynamic infiltration can be influenced by the microenvironment to promote tumor proliferation, survival and metastasis or cancer inhibition. In particular, the cancer microenvironment metabolites can regulate the inflammatory cells to induce a chronic inflammatory response that can be a predisposing condition for CRC retention. In addition, some nutritional components might contribute to a chronic inflammatory condition by regulating various immune and inflammatory pathways. Besides that, diet strongly modulates the gut microbiota composition, which has a key role in maintaining gut homeostasis and is associated with the modulation of host inflammatory and immune responses. Therefore, diet has a fundamental role in CRC initiation, progression and prevention. In particular, functional foods such as probiotics, prebiotics and symbiotics can have a potentially positive effect on health beyond basic nutrition and have anti-inflammatory effects. In this review, we discuss the influence of diet on gut microbiota composition, focusing on its role on gut inflammation and immunity. Finally, we describe the potential benefits of using probiotics and prebiotics to modulate the host inflammatory response, as well as its application in CRC prevention and treatment.

Pesticide dichorvos induces early solid Ehrlich tumoral development associated with a non-protective pro-inflammatory response.

Prolonged exposure to dichlorvos (DDVP), a common pesticide used for food crops, has been related to the development of infections and malignancies. Macrophages are used as bioindicators of immunotoxicity; thus, evaluation of their activity in solid Ehrlich tumor-bearing mice (TBM) may be useful to evaluate the influence of pesticides on human health. To investigate the effects of low DDVP doses, Swiss mice were divided into the following groups: the DDVP group, composed of mice fed diets containing 10 mg/kg of DDVP; the TBM group, consisting of mice subcutaneously inoculated with 107 tumor cells/100 µl and fed a basal diet; the DDVP-TBM group, consisting of mice previously fed DDVP-containing diets for 28 days and then subcutaneously inoculated with tumor cells; and the control (CTRL) group, composed of mice fed a basal diet. After 7 and 21 days of tumor inoculation, the mice were euthanized; and after necroscopic examination, the neoplastic mass, organs, and intraperitoneal fluid were collected. Adherent peritoneal cells were cultivated to determine the production of H2O2 and TNF. Altogether, our results indicate that even at low doses, the intake of DDVP caused weight loss and increased tumor mass, which were associated with H2O2 production and high levels of TNF, a pro-inflammatory cytokine. These data are important as the exposure to pesticides, even at low doses, could potentially hinder the immune response against tumors and, consequently, create favorable conditions for their development.

Low Concentration of 5-Fluorouracil Increases the Effectiveness of Tumor RNA to Activate Murine Dendritic Cells.

AIM: Considering the central role of dendritic cells (DCs) on the development of an antitumor immune response, in this study we used a murine model to evaluate how DC transfection with drug-treated tumor cell RNA changes their phenotype, and whether transfection enhances the in vivo effectiveness of a DC-based antitumor vaccine. MATERIALS AND METHODS: MC-38 colorectal tumor cells were pretreated with the minimum effective concentration of 5-fluorouracil (5-FU), then their total RNA was extracted and transfected into DCs. These DCs were inoculated into C57Bl/6 mice bearing subcutaneous MC-38 tumor. RESULTS: DC transfection with drug-treated tumor RNA increases the percentages of CD40+ (from 37.6% to 61.4%), CD86+ (from 39.8% to 53.4%), and major histocompatibility complex class II+ (from 51.2% to 75.3%) cells, whereas significantly increases the in vivo generation of interferon-γ producer lymphocytes. CONCLUSION: These results reinforce our view that treatment of tumor cells with 5-FU induces transcriptional changes that can be transferred to DCs by RNA transfection, enhancing their ability to stimulate an antitumor response.

Macrophage activity and histopathology of the lymphohematopoietic organs in male Wistar rats orally exposed to single or mixed pesticides.

The noxious effects of low or effective dose exposure to single or mixed pesticides on macrophage activity and the lymphohematopoietic organs were investigated. Male Wistar rats were orally exposed to dichlorvos, dicofol, endosulfan, dieldrin and permethrin, either as single or combined mixtures during a 28-day study containing eight groups: one group received a semipurified diet (non-treated); two groups received a semipurified diet containing low dose mixture (dieldrin 0.025 mg/kg, endosulfan, 0.6 mg/kg, dicofol 0.22 mg/kg, dichlorvos 0.23 mg/kg, permethrin 5 mg/kg) or an effective dose mixture (dichlorvos 2.3 mg/kg, dicofol 2.5 mg/kg, endosulfan 2.9 mg/kg, dieldrin 0.05 mg/kg and permethrin 25.0 mg/kg), respectively; the other five groups received a semipurified diet containing each single pesticide in effective doses. At sacrifice, the thymus, spleen, mesenteric lymph nodes, Payer's patches and bone marrow were removed for histological analysis. Peritoneal macrophages were obtained to determine the phagocytosis and spreading indexes and tumoral necrosis factor alpha (TNF-α), nitric oxide (NO) and H2O2 production. Exposure to pesticide mixtures did not alter the percentage of macrophage phagocytosis and spreading, TNF-α production or the NO and H2O2 release when compared to the non-treated group. Neither was there any apparent evidence that a pesticide mixture at low or effective doses altered the histological structure of the lymphohematopoietic organs. The findings indicate that short-term treatment with pesticide mixtures did not induce an apparent immunotoxic effect in male Wistar rats.