Novel Podophyllotoxin Derivatives as Potential Tubulin Inhibitors: Design, Synthesis, and Antiproliferative Activity Evaluation.

A number of podophyllotoxin derivatives (3A-3J) had been designed and synthesized, and their biological activities were evaluated in this study. Moreover, the antiproliferation activities of these compounds against four human cancer cell lines (HepG2, HeLa, A549, and MCF-7) were also tested. The results indicated that the most promising compound 3D displayed potent inhibitory activity over the four human cancer cell lines and was further demonstrated to have potent tubulin polymerization inhibitory effects without damaging the non-cancer cells. Additionally, 3D was verified to effectively interfere with tubulin and could prevent the mitosis of cancer cells, leading to cell cycle arrest and eventually inducing apoptosis in a dose- and time-dependent manner. Moreover, the Western blotting and siRNA results showed that Bcl-2 was downregulated in HepG2 cells treated with 3D. Finally, the molecular docking simulation results revealed that 3D could fit well in the colchicine-binding pocket. Taken together, this study has provided certain novel antitubulin agents for possible cancer chemotherapy.

Enrichments/Derichments of Root-Associated Bacteria Related to Plant Growth and Nutrition Caused by the Growth of an EPSPS-Transgenic Maize Line in the Field.

During the past decades, the effects of the transgenic crops on soil microbial communities have aroused widespread interest of scientists, which was mainly related to the health and growth of plants. In this study, the maize root-associated bacterial communities of 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) transgenic glyphosate-tolerant (GT) maize line CC-2 (CC2) and its recipient variety Zhengdan958 (Z958) were compared at the tasseling and flowering stages by high-throughput sequencing of V3-V4 hypervariable regions of 16S rRNA gene (16S rDNA) amplicons via Illumina MiSeq. In addition, real-time quantitative PCR (qPCR) was also performed to analyze the nifH gene abundance between CC2 and Z958. Our results showed no significant difference in alpha/beta diversity of root-associated bacterial communities at the tasseling or flowering stage between CC2 and Z958 under field growth conditions. The relative abundances of the genera Bradyrhizobium and Bacillus including species B. cereus and B. muralis were significantly lower in the roots of CC2 than that of Z985 under field conditions. Both these species are regarded as plant growth promoting bacteria (PGPB), as they belong to both nitrogen-fixing and phosphate-solubilizing bacterial genera. The comparison of the relative abundance of nitrogen-fixing/phosphate-solubilizing bacteria at the class, order or family levels indicated that only one class Bacilli, one order Bacillales and one family Bacillaceae were found to be significantly lower in the roots of CC2 than that of Z985. These bacteria were also enriched in the roots and rhizospheric soil than in the surrounding soil at both two stages. Furthermore, the class Betaproteobacteria, the order Burkholderiales, the family Comamonadaceae, and the genus Acidovorax were significantly higher in the roots of CC2 than that of Z985 at the tasseling stage, meanwhile the order Burkholderiales and the family Comamonadaceae were also enriched in the roots than in the rhizospheric soil at both stages. Additionally, the nifH gene abundance at the tasseling stage in the rhizosphere soil also showed significant difference. The relative abundance of nifH gene was higher in the root samples and lower in the surrounding soil, which implicated that the roots of maize tend to be enriched in nitrogen-fixing bacteria.

Identification of Major Rhizobacterial Taxa Affected by a Glyphosate-Tolerant Soybean Line via Shotgun Metagenomic Approach.

The worldwide commercial cultivation of transgenic crops, including glyphosate-tolerant (GT) soybeans, has increased widely during the past 20 years. However, it is accompanied with a growing concern about potential effects of transgenic crops on the soil microbial communities, especially on rhizosphere bacterial communities. Our previous study found that the GT soybean line NZL06-698 (N698) significantly affected rhizosphere bacteria, including some unidentified taxa, through 16S rRNA gene (16S rDNA) V4 region amplicon deep sequencing via Illumina MiSeq. In this study, we performed 16S rDNA V5-V7 region amplicon deep sequencing via Illumina MiSeq and shotgun metagenomic approaches to identify those major taxa. Results of these processes revealed that the species richness and evenness increased in the rhizosphere bacterial communities of N698, the beta diversity of the rhizosphere bacterial communities of N698 was affected, and that certain dominant bacterial phyla and genera were related to N698 compared with its control cultivar Mengdou12. Consistent with our previous findings, this study showed that N698 affects the rhizosphere bacterial communities. In specific, N698 negatively affects Rahnella, Janthinobacterium, Stenotrophomonas, Sphingomonas and Luteibacter while positively affecting Arthrobacter, Bradyrhizobium, Ramlibacter and Nitrospira.