Glioblastoma multiforme (GBM) is the most malignant and aggressive primary brain tumor in adults. Despite concerted efforts to improve current therapies, the prognosis of glioblastoma remains very poor. Alantolactone, a sesquiterpene lactone compound, has been reported to exhibit antifungal, antibacteria, antihelminthic, and anticancer properties. In this study, we found that alantolactone effectively inhibits growth and triggers apoptosis in glioblastoma cells in a time‐ and dose‐dependent manner. The alantolactone‐induced apoptosis was found to be associated with glutathione (GSH) depletion, reactive oxygen species (ROS) generation, mitochondrial transmembrane potential dissipation, cardiolipin oxidation, upregulation of p53 and Bax, downregulation of Bcl‐2, cytochrome c release, activation of caspases (caspase 9 and 3), and cleavage of poly (ADP‐ribose) polymerase. This alantolactone‐induced apoptosis and GSH depletion were effectively inhibited or abrogated by a thiol antioxidant, N‐acetyl‐L‐cysteine, whereas other antioxidant (polyethylene glycol (PEG)‐catalase and PEG‐superoxide‐dismutase) did not prevent apoptosis and GSH depletion. Alantolactone treatment inhibited the translocation of NF‐κB into nucleus; however, NF‐κB inhibitor, SN50 failed to potentiate alantolactone‐induced apoptosis indicating that alantolactone induces NF‐κB‐independent apoptosis in glioma cells. These findings suggest that the sensitivity of tumor cells to alantolactone appears to results from GSH depletion and ROS production. Furthermore, our in vivo toxicity study demonstrated that alantolactone did not induce significant hepatotoxicity and nephrotoxicity in mice. Therefore, alantolactone may become a potential lead compound for future development of antiglioma therapy. © © 2012 IUBMB Life, 64(9): 783–794, 2012

The early maize (Zea mays) seed undergoes several developmental stages after double fertilization to become fully differentiated within a short period of time, but the genetic control of this highly dynamic and complex developmental process remains largely unknown. Here, we report a high temporal-resolution investigation of transcriptomes using 31 samples collected at an interval of 4 or 6 h within the first six days of seed development. These time-course transcriptomes were clearly separated into four distinct groups corresponding to the stages of double fertilization, coenocyte formation, cellularization, and differentiation. A total of 22,790 expressed genes including 1415 transcription factors (TFs) were detected in early stages of maize seed development. In particular, 1093 genes including 110 TFs were specifically expressed in the seed and displayed high temporal specificity by expressing only in particular period of early seed development. There were 160, 22, 112, and 569 seed-specific genes predominantly expressed in the first 16 h after pollination, coenocyte formation, cellularization, and differentiation stage, respectively. In addition, network analysis predicted 31,256 interactions among 1317 TFs and 14,540 genes. The high temporal-resolution transcriptome atlas reported here provides an important resource for future functional study to unravel the genetic control of seed development.

Isoalantolactone, a sesquiterpene lactone compound possesses antifungal, antibacteria, antihelminthic and antiproliferative activities. In the present study, we found that isoalantolactone inhibits growth and induces apoptosis in pancreatic cancer cells. Further mechanistic studies revealed that induction of apoptosis is associated with increased generation of reactive oxygen species, cardiolipin oxidation, reduced mitochondrial membrane potential, release of cytochrome c and cell cycle arrest at S phase. N-Acetyl Cysteine (NAC), a specific ROS inhibitor restored cell viability and completely blocked isoalantolactone-mediated apoptosis in PANC-1 cells indicating that ROS are involved in isoalantolactone-mediated apoptosis. Western blot study showed that isoalantolactone increased the expression of phosphorylated p38 MAPK, Bax, and cleaved caspase-3 and decreased the expression of Bcl-2 in a dose-dependent manner. No change in expression of phosphorylated p38 MAPK and Bax was found when cells were treated with isoalantolactone in the presence of NAC, indicating that activation of these proteins is directly dependent on ROS generation. The present study provides evidence for the first time that isoalantolactone induces ROS-dependent apoptosis through intrinsic pathway. Furthermore, our in vivo toxicity study demonstrated that isoalantolactone did not induce any acute or chronic toxicity in liver and kidneys of CD1 mice at dose of 100 mg/kg body weight. Therefore, isoalantolactone may be a safe chemotherapeutic candidate for the treatment of human pancreatic carcinoma.

Drought is a major abiotic stress that affects plant growth, production, and survival. Plants have evolved sophisticated and highly complex reactions to drought stress, including large-scale transcriptome reconfiguration. Foxtail millet (Setaria italica) is a member of the Poaceae family. Because of its outstanding tolerance to drought stress foxtail millet has the potential to become a new model organism. To enrich our knowledge of the processes that contribute to drought resistance, we have used a deep sequencing approach to generate a genome-wide transcriptome of foxtail millet after exposure to simulated drought stress. A large number of differentially expressed genes were characterized; in particular, we examined the roles of small interfering RNAs (siRNAs) and long noncoding RNAs (lncRNAs) in response to a water-deficit condition. These RNAs have remained largely unexplored in previous studies of stress-induced transcriptomes. We found that the reduced levels of 24-nt siRNA flanking genes were associated, for the most part, with proximal up-regulated genes, indicating a potential effect of 24-nt siRNAs on drought-regulated gene expression. Several lncRNAs that responded to the simulated drought stress were also identified, and we found that one of them shared sequence conservation and colinearity with its counterpart in sorghum (Sorghum bicolor). Our findings provide new insights into drought-induced changes in the foxtail millet transcriptome.