Japonicone A Suppresses Growth of Burkitt Lymphoma Cells through Its Effect on NF-κB

Abstract

Purpose: NF-kB, a transcriptional regulator of diverse genes involved in cell survival, proliferation, adhesion, and apoptosis, has been implicated in various malignancies. We discovered a potent natural NF-kB inhibitor, Japonicone A, from the traditional herb Inula japonica Thunb, evaluated its preclinical pharmacology and therapeutic activity, and investigated the underlying mechanisms of action for its antitumor activity.Experimental Design: Various types of cancer and normal cells were exposed to Japonicone A for cytotoxicity screening, followed by determination of cell apoptosis and cell-cycle arrest. Western blotting, immunostaining, and gene reporter assay were used to analyze NF-kB activity. Two xenograft models were used for therapeutic efficacy evaluation.Results: Japonicone A killed cancer cells but had low cytotoxicity to normal cells. Burkitt lymphoma cells were particularly sensitive. Japonicone A inhibited the growth and proliferation of Raji, BJAB, and NAMALWA lymphoma cells and resulted in G 2 -M phase arrest and apoptosis. Furthermore, exposure of cells to Japonicone A caused inactivation of the TNF-a-TAK1-IKK-NF-kB axis and inhibition of TNFa-stimulated NF-kB activity and nuclear translocation, followed by downregulation of NF-kB target genes involved in cell apoptosis (Bcl-2, Bcl-xL, XIAP, TRAF2) and in the cell cycle and growth (cyclin D, c-Myc). Moreover, Japonicone A inhibited local growth and dissemination of cancer cells to multiple organs in vivo.Conclusion: Japonicone A exerts significant anticancer effects on Burkitt lymphoma cells in vitro and in vivo through targeting of the NF-kB signaling cascade. These results highlight the potential of Japonicone A as a chemotherapeutic agent and warrant its development as a therapy for lymphomas.

Japonicone A inhibits the growth of non-small cell lung cancer cells via mitochondria-mediated pathways

“…Traditional herbal medicines containing various biologically active natural compounds are believed to have therapeutic efficacy with minimal adverse effects [7]. Japonicone A is a natural product isolated from the aerial part of Inula japonica Thunb., which is a traditional medicine used to treat digestive disorders, bronchitis, inflammation, and bacterial and viral infections (including hepatitis) [8].…”

“…and antagonize its proinflammatory activities in vivo without impairing host antiviral immunity [9]. Further studies have demonstrated that japonicone A displayed potent anticancer effects on Burkitt lymphoma cells in vitro and in vivo through targeting the NF-κB signaling cascade [7]. However, the effects of japonicone A and its mechanism of action on human NSCLC cells have never been elucidated.…”

Preclinical Efficacy and Safety Assessment of Artemisinin-Chemotherapeutic Agent Conjugates for Ovarian Cancer

“…Cell viability was determined with CCK-8 kits, as described previously (Li et al, 2013a, Li et al, 2013b). Briefly, cells were seeded in 96-well plates and were treated either with compounds at serial concentrations or for various times.…”

“…PI staining was used to detect the effects of ARS-related compounds on cell cycle distribution (Li et al, 2013a, Li et al, 2013b). In brief, after incubation with the compounds, A2780 and OVCAR3 cells were harvested and fixed with 70% ethanol, followed by RNase digestion and staining with PI (50 μg/ml).…”

Metabolomic profiling of cancer cells to Aloe vera extract by 1HNMR spectroscopy

“…Raji cells are a series of cell lines derived from B lymphocyte of a patient with Burkitt's lymphoma (BL) which is an aggressive form of B cell non Hodgkin's lymphoma [5] with reports of chemotherapy resistance.…”