Aqueous extracts from Tenebrio molitor larval and pupal stages inhibit early hepatocarcinogenesis in vivo.

Hepatocellular carcinoma (HCC), which is the most frequent primary liver malignancy, is ranked as the sixth most common cancer and the third leading cause of cancer-related deaths worldwide, with its incidence expected to continue rising. One of the reasons is that most patients are diagnosed at an advanced stage when therapeutic options are ineffective. The development of HCC is attributed to a chronic exposition to either one or a combination of low amounts of different hepatotoxins, such as in hepatitis virus infection, alcohol consumption, aflatoxin from contaminated foods, metabolic factors, and exposure to chemical carcinogens from tobacco smoke (Forner et al., 2018). Integrative studies combining exome sequencing, transcriptome analysis, and the genomic characterization of HCC have shown that these etiological factors may raise the frequency of particular genetic alterations, resulting in intra-tumor heterogeneity that presents a huge challenge for treatment. For example, mutations in the catenin ß-1 (CTNNB1) gene (a proto-oncogene in the WNT signaling pathway that encodes the ß|-catenin transcription factor) are strongly associated with alcohol-related HCC, whereas mutations in the telomerase reverse transcriptase (TERT) promoter and tumor protein p53 (TP53) genes are the most commonly observed in hepatitis B virus (HBV)|-associated HCC (Calderaro et al., 2017; Cancer Genome Atlas Research Network, 2017). The above findings emphasize the molecular diversity of HCC and the associations of different etiologies with distinct mechanisms in HCC progression. Consequently, prevention strategies are still attractive for HCC management.

Anti-MDR Effects of Quercetin and its Nanoemulsion in Multidrug-Resistant Human Leukemia Cells.

BACKGROUND: Quercetin has potential against the Multidrug Resistance (MDR) phenotype, but with low bioavailability. The increase in the bioavailability can be obtained with nanostructures. OBJECTIVE: To analyze the effects of quercetin and its nanoemulsion on MDR and non-MDR cells. METHODS: We used high-pressure homogenization for nanoemulsion production; Trypan Blue for cytostatic/cytotoxicity assays; Epifluorescence microscope (with specific probes) for apoptosis and DNA damage; Real-Time PCR for gene expression; AutoDock Vina for docking and Flow Cytometry for efflux analysis. Quercetin exerted antiproliferative impact, induced apoptosis, necrosis and DNA damage on cells. RESULTS: Quercetin combined with vincristine showed an effect similar to verapamil (an ABCB1 inhibitor), and docking showed that it binds to ABCB1 in a similar region. Quercetin was also capable of altering ABCB1 gene expression. Quercetin in nanoemulsion maintained the cytotoxic and cytostatic effects of quercetin, which may increase bioavailability. Besides, the unloaded nanoemulsion was able to inhibit per se the efflux activity of ABCB1, demonstrating pharmacological action of this structure. CONCLUSION: Quercetin may be considered as a prospective drug to overcome resistance in cancer cells and its nanoemulsion can be an alternative for in vivo application.