Bisindolylmaleimide alkaloid BMA-155Cl induces autophagy and apoptosis in human hepatocarcinoma HepG-2 cells through the NF-κB p65 pathway.

Bisindolylmaleimides, a series of derivatives of a PKC inhibitor staurosporine, exhibit potential as anti-cancer drugs and have received considerable attention in clinical trials. This study aims to investigate the effects of a bisindolylmaleimide alkaloid 155Cl (BMA-155Cl) with a novel structure on autophagy and apoptosis in human hepatocarcinoma HepG-2 cells in vitro and in vivo. The cell poliferation was assessed with a MTT assay. Autophagy was evaluated by MDC staining and TEM analysis. Apoptosis was investigated using Annexin V-FITC/PI and DAPI staining. The antitumor effects were further evaluated in nude mice bearing HepG-2 xenografts, which received BMA-155Cl (10, 20 mg/kg, ip) for 18 days. Autophagy- and apoptosis-associated proteins and their mRNA levels were examined with Western blotting, immunohistochemistry, and RT-PCR. BMA-155Cl (2.5-20 µmol/L) inhibited the growth of HepG-2 cells with IC50 values of 16.62±1.34, 12.21±0.83, and 8.44±1.82 µmol/L at 24, 48, and 72 h, respectively. Furthermore, BMA-155Cl (5-20 µmol/L) dose-dependently induced autophagy and apoptosis in HepG-2 cells. The formation of autophagic vacuoles was induced by BMA-155Cl (10 µmol/L) at approximately 6 h and peaked at approximately 15 h. Pretreatment with 3-MA potentiated BMA-155Cl-mediated apoptotic cell death. This compound dose-dependently increased the mRNA and protein levels of Beclin-1, NF-κB p65, p53, and Bax, but decreased the expression of IκB and Bcl-2. Pretreatment with BAY 11-7082, a specific inhibitor of NF-κB p65, blocked BMA-155Cl-induced expression of autophagy- and apoptosis-associated proteins. BMA-155Cl administration effectively suppressed the growth of HepG-2 xenografts in vivo, and increased the protein expression levels of LC3B, Beclin-1, NF-κB p65, and Bax in vivo. We conclude that the NF-κB p65 pathway is involved in BMA-155Cl-triggered autophagy, followed by apoptosis in HepG-2 cells in vitro and in vivo. Hence, BMA-155Cl could be a promising pro-apoptotic candidate for developing as a novel anti-cancer drug.

Marine natural products sourced from marine-derived Penicillium fungi.

Marine micro-organisms have been proven to be a major source of marine natural products (MNPs) in recent years, in which filamentous fungi are a vital source of bioactive natural products for their large metagenomes and more complex genetic backgrounds. This review highlights the 390 new MNPs from marine-derived Penicillium fungi during 1991 to 2014. These new MNPs are categorized based on the environment sources of the fungal hosts and their bioactivities are summarized.

Bacterial Microbiome Differences between the Roots of Diseased and Healthy Chinese Hickory (Carya cathayensis) Trees.

Carya cathayensis is an important economic nut tree that is endemic to eastern China. As such, outbreaks of root rot disease in C. cathayensis result in reduced yields and serious economic losses. Moreover, while soil bacterial communities play a crucial role in plant health and are associated with plant disease outbreaks, their diversity and composition in C. cathayensis are not clearly understood. In this study, Proteobacteria, Acidobacteria, and Actinobacteria were found to be the most dominant bacterial communities (accounting for approximately 80.32% of the total) in the root tissue, rhizosphere soil, and bulk soil of healthy C. cathayensis specimens. Further analysis revealed the abundance of genera belonging to Proteobacteria, namely, Acidibacter, Bradyrhizobium, Paraburkholderia, Sphaerotilus, and Steroidobacter, was higher in the root tissues of healthy C. cathayensis specimens than in those of diseased and dead trees. In addition, the abundance of four genera belonging to Actinobacteria, namely, Actinoallomurus, Actinomadura, Actinocrinis, and Gaiella, was significantly higher in the root tissues of healthy C. cathayensis specimens than in those of diseased and dead trees. Altogether, these results suggest that disruption in the balance of these bacterial communities may be associated with the development of root rot in C. cathayensis, and further, our study provides theoretical guidance for the isolation and control of pathogens and diseases related to this important tree species.