Paeonol inhibits B16F10 melanoma metastasis In vitro and In Vivo via disrupting proinflammatory cytokines‐mediated NF‐κB and STAT3 pathways

Abstract

Cancer related inflammation (CRI) is now recognized as the seventh hallmark in the pathogenesis of many types of malignancies. Paeonol, a natural phenolic component isolated from the root bark of Paeonia moutan, has significant antiinflammatory activity. Recently, accumulating body of research has revealed potent anti-tumor effects mediated by paeonol. However, little is known about its anticancer mechanism on the basis of CRI. In this study, we observed that paeonol exerted direct anticancer activity through inhibition of cell proliferation, induction of apoptosis, and evident antiinflammatory effects by reducing proinflammatory cytokines secretion (TNF-a, IL-1b, IL-6, and TGF-b) in the conditioned medium of B16F10 mouse melanoma cells. Interestingly, we found that paeonol significantly reversed motility phenotypes in TNF-a-or IL-6-induced B16F10 singe cell and collective migration and invasion in vitro, which were related to affecting epithelial-to-mesenchymal transition (EMT) makers and MMPs expression. In particular, paeonol disrupted both TNFa-activated NF-jB and IL-6-activated STAT3 signaling pathways in B16F10 cells. EMSA and luciferase assays showed that paeonol abrogated NF-jB binding and NF-jB-driven promoter activity in the presence of TNF-a. Finally, we showed that paeonol attenuated B16F10 spontaneous lung metastases in C57/BL6J mice with down-regulated levels of serum proinflammatory cytokines. Therefore, paeonol possessed antitumor activity in melanoma cells and mice model by 778IUBMB Life interruption of the aggressive feedback through proinflammatory cytokines mediated NF-jB and STAT3 signaling activation. These findings provide a novel treatment strategy that paeonol might be a promising versatile adjuvant therapy for cancer related inflammation. V C 2015 IUBMB Life, 67(10): [778][779][780][781][782][783][784][785][786][787][788] 2015

SOCS1 favors the epithelial-mesenchymal transition in melanoma, promotes tumor progression and prevents antitumor immunity by PD-L1 expression

“…showed that the expression of PD-L1 attenuates the phosphorylation of p42/ERK2, suggesting that PD-L1 may mediate the induction of Treg cells by modulating ERK2 activity and MAP kinase signaling cascade. The increase in PD-L1 expression in tumor cells can induce Foxp3 + Treg cells increasing the suppression of antitumor T-cell responses and thus allowing tumor progression47. Our data showed a systemic reduction of IL-17A and IL-10 cytokines and a significant decrease of FoxP3 + Treg cells in spleen and lung tissues of mice that received a subcutaneous inoculation of B16shR-SOCS1 cells.…”

<p>Paeonol Inhibits Pancreatic Cancer Cell Migration and Invasion Through the Inhibition of TGF-β1/Smad Signaling and Epithelial-Mesenchymal-Transition</p>

“…It has been reported that the cancer growth inhibition effects of Paeonol involve COX-2/PGE2, TNF-α, caspase-cascade, MAPK pathway, PI3K-AKT pathway, etc. 14,17,41,42 Contrary to its relatively well established anti-proliferative and apoptosis-inducing effects in the literature, relatively few works have been published, documenting the role of Paeonol in metastasis. The anti-metastatic activities of Paeonol on human fibrosarcoma and chondrosarcoma cells have been previously reported.…”

Paeonol extracted from Paeonia suffruticosa Andr. ameliorated UVB‐induced skin photoaging via DLD/Nrf2/ARE and MAPK/AP‐1 pathway

“…PA was detected in PSR with high concentration, indicating PA the major active ingredient in PSR. Although there are not any studies demonstrating anti‐skin aging effects, PA has been reported to inhibit tyrosinase activity and melanin synthesis (L. Zhang et al, ) and to mitigate smoking‐induced lung inflammation by suppressing ROS‐sensitive inflammatory signaling (Liu et al, ). Given its known effects on other pathologies, PS could be a promising candidate to prevent premature skin triggered by oxidative stress.…”

“…Its main uses involve clearing heat, cooling blood, and other similar purposes (He, Peng, Dan, Peng, & Xiao, 2014). This study sought to evaluate the potential effects of PS in mitigating UVB- Zhang et al, 2015) and to mitigate smokinginduced lung inflammation by suppressing ROS-sensitive inflammatory signaling (Liu et al, 2014). Given its known effects on other pathologies, PS could be a promising candidate to prevent premature skin triggered by oxidative stress.…”