Wogonin as a targeted therapeutic agent for EBV (+) lymphoma cells involved in LMP1/NF-κB/miR-155/PU.1 pathway

Abstract

BackgroundWogonin is an encouraging choice for clinical use owing to its potent anti-tumor and anti-inflammatory effects with the high safety profile. However, wogonin for targeted therapy of lymphoma was not well addressed. In this study, we focused on its anticancer effect alongside with the underlying mechanisms for targeted therapy in EBV-positive lymphoma. This will facilitate its introduction to clinical use, which is planned in the near future.MethodsCell proliferation was studied by CCK8. Flow cytometry was used to analyze the apoptosis and the cycle arrest of cells. Further, we also used immunofluorescent staining to detect the morphologic changes of the apoptotic cells. The expression of LMP1/miR-155/p65/pp65/PU.1 was evaluated by quantitative real-time PCR (qRT-PCR) and western blot, while that of NF-κB was analyzed by EMSA. At last, immunohistochemical staining was applied to assess the expression of target proteins and relevant molecules.ResultsIn vitro, wogonin induced the apoptosis of Raji cells by downregulating the expression of NF-κB through LMP1/miR-155/NF-κB/PU.1 pathway, which was in a dose and time-dependent manner. In vivo, wogonin could suppress tumor growth, associated with the downregulation of ki67, p65 and upregulation of PU.1.ConclusionsWogonin could suppress tumor growth and induce cell apoptosis by inhibiting the expression of NF-κB. Taken these findings, we concluded that wogonin could be a potential targeted therapeutic agent for EBV-positive lymphoma with the expression of LMP1 through the pathway of LMP1/NF-κB/miR-155/PU.1.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3145-4) contains supplementary material, which is available to authorized users.

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

“…Wogonin also enhances ROS production in human glioma U251 and U87, pancreatic cancer Panc-1 and Colo-357, and NSCLC A549 cells [711,721,729]. Moreover, it inhibits cell growth and induces apoptosis through NF-κB suppression in Epstein-Barr virus-positive lymphoma cells [730], and suppresses cell proliferation and invasion through NF-κB/Bcl-2 and EGFR pathways in human hepatocellular carcinoma HepG2 and Bel-7402 cells [717].…”

Regulation of cell signaling pathways by Wogonin in different cancers: Mechanistic review

“…NF-κB-mediated upregulation of miR-155 and blocked apoptosis. Wogonin impaired NF-κBdriven upregulation of miR-155 and induced apoptotic cell death 66 .…”

Natural Products and Their Derivatives against Human Herpesvirus Infection

“…Then, 14 dose-dependently demonstrated antiproliferative effects, induced apoptosis at the G1 phase, and inhibited NF-κB activity in Raji cells. The compound also attenuated the average tumor size and weight in BALB⁄c nude mice [82]. The mice received intraperitoneal injection of 14 with a minimal toxic concentration of 8 mg/kg every 2 days for 2 weeks.…”

“…For example, 3 inhibited tumor formation in NOD/SCID mice via the MAPK/ERK signaling pathway and reduced cell viability through the p53-related signaling pathway by targeting XAF1 and GADD45α expression via a mitochondria-dependent pathway [55,56]. Treatment with 14 attenuated the average tumor size and weight in BALB⁄c nude mice [82]. Then, 21 can efficiently reduce the growth of B95-8-induced B lymphoma and downregulate LANA1 expression, and viral replication in PEL cells in mice [95,96,98].…”