BackgroundHere, we determined in vitro antioxidant activity, total phenols and flavonoids and evaluated antiproliferative activity of three medicinal plant extracts: Trigonella foenum-graecum (Fenugreek), Cassia acutifolia (Senna) and Rhazya stricta (Harmal).MethodsThe leaves of the three medicinal plants were extracted with 70% ethanol. Antioxidant activities of the extracts were determined by using DPPH (1,1-diphenyl-2-picrylhydrazyl) assay. Total flavonoid and phenolic contents were determined using colorimetric assays. MTT assay was used to estimate the antiproliferative activities of the extracts against human hepatoma (HepG2) cancer cell line. In addition, the effects of R. stricta extract on cell cycle, colony formation, and wound healing of HepG2 cells and tube formation of HUVEC cells were assessed.ResultsPercentage inhibition of DPPH scavenging activity were dose-dependent and ranged between (89.9% ± 0.51) and (28.6% ± 2.07). Phenolic contents ranged between (11.5 ± 0.013) and (9.7 ± 0.008) mg GAE/g while flavonoid content ranged between (20.8 ± 0.40) and (0.12 ± 0.0.01) mg QE/g. Antiproliferative results of the extracts were found to be consistent with their antioxidant activity. Among the extracts evaluated, that of R. stricta showed the best antioxidant, antiproliferative and antimetastatic activities at low concentration. It also inhibited the colony-formation capacity of HepG2 cells and exhibited antiangiogenic activity. Cell cycle analysis showed significant arrest of cells at G2/M phase 12 and 48 h after treatment and significant arrest at G1/S phase after 24 h of treatment. Consistent data were observed in western blot analysis of protein levels of Cdc2 and its cyclin partners.ConclusionsThese findings introduce R. stricta as a potentially useful anti-metastatic agent and a novel potential anti-tumour agent for hepatocellular carcinoma (HCC) treatment.Electronic supplementary materialThe online version of this article (10.1186/s12906-018-2285-7) contains supplementary material, which is available to authorized users.

Taken together, our findings introduce crocin as a candidate chemopreventive agent against HCC.

Extracellular vesicles (EVs) are emerging as potent and intricate intercellular communication networks. From their first discovery almost forty years ago, several studies have bolstered our understanding of these nano-vesicular structures. EV subpopulations are now characterized by differences in size, surface markers, cargo, and biological effects. Studies have highlighted the importance of EVs in biology and intercellular communication, particularly during immune and tumor interactions. These responses can be equally mediated at the proteomic and epigenomic levels through surface markers or nucleic acid cargo signaling, respectively. Following the exponential growth of EV studies in recent years, we herein synthesize new aspects of the emerging immune–tumor EV-based intercellular communications. We also discuss the potential role of EVs in fundamental immunological processes under physiological conditions, viral infections, and tumorigenic conditions. Finally, we provide insights on the future prospects of immune–tumor EVs and suggest potential avenues for the use of EVs in diagnostics and therapeutics.

The tumor microenvironment and its contribution to tumorigenesis has been a focal highlight in recent years. A two-way communication between the tumor and the surrounding microenvironment sustains and contributes to the growth and metastasis of tumors. Progression and metastasis of hepatocellular carcinoma (HCC) have been reported to be exceedingly influenced by diverse microenvironmental cues. In this study, we present a 3D-culture model of liver cancer to better mimic in vivo tumor settings. By creating novel 3D co-culture model that combines free-floating and scaffold-based 3D-culture techniques of liver cancer cells and fibroblasts, we aimed to establish a simple albeit reproducible ex vivo cancer microenvironment model that captures tumor-stroma interactions. The model presented herein exhibited unique gene expression and protein expression profiles when compared to 2D and 3D mono-cultures of liver cancer cells. Our results showed that in vivo like conditions cannot be mimicked by simply growing cancer cells as spheroids, but by co-culturing them with 3D fibroblast with which they were able to crosstalk. This was evident by the upregulation of several pathways involved in HCC, and the increase in secreted factors by co-cultured cancer cells, many of which are also involved in tumor-stroma interactions. Compared to the conventional 2D culture, the proposed model exhibits an increase in the expression of genes associated with development, progression, and poor prognosis of HCC. Our results correlated with an aggressive outcome that better mirrors in vivo HCC, and therefore, a more reliable platform for molecular understanding of HCC.