Tumor-suppressive effects of resveratrol have been shown in various types of cancer. However, regulation of tumor microenvironment by resveratrol is still unclear. Recent findings suggest resveratrol can potentiate its tumor-suppressive effect through modulation of the signaling pathways of cellular components (fibroblasts, macrophages and T cells). Also, studies have shown that resveratrol can suppress malignant phenotypes of cancer cells acquired in response to stresses of the tumor microenvironment, such as hypoxia, oxidative stress and inflammation. We discuss the effects of resveratrol on cancer cells in stress environment of tumors as well as interactions between cancer cells and non-cancer cells in this review.

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We aimed to develop a diagnostic model identifying ovarian cancer (OC) from benign ovarian tumors using metagenomic data from serum microbe-derived extracellular vesicles (EVs). We obtained serum samples from 166 patients with pathologically confirmed OC and 76 patients with benign ovarian tumors. For model construction and validation, samples were randomly divided into training and test sets in the ratio 2:1. Isolation of microbial EVs from serum samples of the patients and 16S rDNA amplicon sequencing were carried out. Metagenomic and clinicopathologic data-based OC diagnostic models were constructed in the training set and then validated in the test set. There were significant differences in the metagenomic profiles between the OC and benign ovarian tumor groups; specifically, genus Acinetobacter was significantly more abundant in the OC group. More importantly, Acinetobacter was the only common genus identified by seven different statistical analysis methods. Among the various metagenomic and clinicopathologic data-based OC diagnostic models, the model consisting of age, serum CA-125 levels, and relative abundance of Acinetobacter showed the best diagnostic performance with the area under the receiver operating characteristic curve of 0.898 and 0.846 in the training and test sets, respectively. Thus, our findings establish a metagenomic analysis of serum microbe-derived EVs as a potential tool for the diagnosis of OC.

The interaction of immune checkpoint molecules in the tumor microenvironment reduces the anti-tumor immune response by suppressing the recognition of T cells to tumor cells. Immune checkpoint inhibitor (ICI) therapy is emerging as a promising therapeutic option for cancer treatment. However, modulating the immune system with ICIs still faces obstacles with severe immunogenic side effects and a lack of response against many cancer types. Plant-derived natural compounds offer regulation on various signaling cascades and have been applied for the treatment of multiple diseases, including cancer. Accumulated evidence provides the possibility of efficacy of phytochemicals in combinational with other therapeutic agents of ICIs, effectively modulating immune checkpoint-related signaling molecules. Recently, several phytochemicals have been reported to show the modulatory effects of immune checkpoints in various cancers in in vivo or in vitro models. This review summarizes druggable immune checkpoints and their regulatory factors. In addition, phytochemicals that are capable of suppressing PD-1/PD-L1 binding, the best-studied target of ICI therapy, were comprehensively summarized and classified according to chemical structure subgroups. It may help extend further research on phytochemicals as candidates of combinational adjuvants. Future clinical trials may validate the synergetic effects of preclinically investigated phytochemicals with ICI therapy.

Resveratrol (3,4′,5-trans-trihydroxystilbene) and piceatannol (3,3′,4′,5-trans-tetraphydroxystilbene) are major stilbene compounds that are predominantly present in various natural foods, such as berries and fruits. Both phytochemical compounds are consumed as dietary supplements to prevent various metabolic diseases and for their anti-aging properties. Adipose-derived stem cells from human visceral adipose tissue (vASCs) are a useful in vitro model for evaluating their adipogenic effect. Treatment with resveratrol and piceatannol significantly inhibited lipid accumulation in vASCs. Their effective concentrations were 5, 10, and 20 μM for inhibiting adipogenesis of vASCs. Interestingly, despite the similar chemical structures of the two compounds, piceatannol showed a higher anti-adipogenic effect at 20 μM than resveratrol in vASCs. Moreover, the inhibitory capacity of lipid droplet generation was higher for piceatannol at 20 μM than that of resveratrol. Piceatannol significantly attenuated the expression level of adipogenic markers (e.g., CCAAT/enhanced binding protein α (C/EBPα), peroxisome proliferator-activated receptor γ (PPARγ), and adipocyte fatty acid binding protein (aP2)) compared to resveratrol at the mRNA and protein levels. These results suggest that piceatannol is a superior anti-adipogenic compound compared to resveratrol in the vASC model of visceral obesity.