Tunicamycin enhances TRAIL-induced apoptosis by inhibition of cyclin D1 and the subsequent downregulation of survivin

Hai-Yan Zhang,Zhen-Xian Du,Bao-Qin Liu,Yan-Yan Gao,Xin Meng,Yifu Guan,Wei-Wei Deng,Hua-Qin Wang 생화학분자생물학회 2009 Experimental and molecular medicine Vol.41 No.5

TNF-related apoptosis-inducing ligand (TRAIL) has been proposed as a promising cancer therapy that preferentially induces apoptosis in cancer cells, but not most normal tissues. However, many cancers are resistant to TRAIL by mechanisms that are poorly understood. In this study, we showed that tunicamycin, a naturally occurring antibiotic, was a potent enhancer of TRAIL-induced apoptosis through downregulation of survivin. The tunicamycin-mediated sensitization to TRAIL was efficiently reduced by forced expression of survivin, suggesting that the sensitization was mediated at least in part through inhibition of survivin expression. Tunicamycin also repressed expression of cyclin D1, a cell cycle regulator commonly overexpressed in thyroid carcinoma. Furthermore, silencing cyclin D1 by RNA interference reduced survivin expression and sensitized thyroid cancer cells to TRAIL; in contrast, forced expression of cyclin D1 attenuated tunicamycin-potentiated TRAIL-induced apoptosis via over-riding downregulation of survivin. Collectively, our results demonstrated that tunicamycin promoted TRAIL-induced apoptosis, at least in part, by inhibiting the expression of cyclin D1 and subsequent survivin. Of note, tunicamycin did not sensitize the differentiated thyroid epithelial cells to TRAIL-induced apoptosis. Thus, combined treatment with tunicamycin and TRAIL may offer an attractive strategy for safely treating resistant thyroid cancers. TNF-related apoptosis-inducing ligand (TRAIL) has been proposed as a promising cancer therapy that preferentially induces apoptosis in cancer cells, but not most normal tissues. However, many cancers are resistant to TRAIL by mechanisms that are poorly understood. In this study, we showed that tunicamycin, a naturally occurring antibiotic, was a potent enhancer of TRAIL-induced apoptosis through downregulation of survivin. The tunicamycin-mediated sensitization to TRAIL was efficiently reduced by forced expression of survivin, suggesting that the sensitization was mediated at least in part through inhibition of survivin expression. Tunicamycin also repressed expression of cyclin D1, a cell cycle regulator commonly overexpressed in thyroid carcinoma. Furthermore, silencing cyclin D1 by RNA interference reduced survivin expression and sensitized thyroid cancer cells to TRAIL; in contrast, forced expression of cyclin D1 attenuated tunicamycin-potentiated TRAIL-induced apoptosis via over-riding downregulation of survivin. Collectively, our results demonstrated that tunicamycin promoted TRAIL-induced apoptosis, at least in part, by inhibiting the expression of cyclin D1 and subsequent survivin. Of note, tunicamycin did not sensitize the differentiated thyroid epithelial cells to TRAIL-induced apoptosis. Thus, combined treatment with tunicamycin and TRAIL may offer an attractive strategy for safely treating resistant thyroid cancers.

Isoindolin-1-ones from the stems of Nicotiana tabacum and their antiviral activities

Guang-Yu Yang,Jia-Meng Dai,Zhen-Jie Li,Jin Wang,Feng-Xian Yang,Xin Liu,Jing Li,Qian Gao,Xue-Mei Li,Yin-Ke Li,Wei-Guang Wang,Min Zhou,Qiu-Fen Hu 대한약학회 2022 Archives of Pharmacal Research Vol.45 No.8

In previous studies, several isoindolin-1-oneanalogs that exhibited signifi cant anti-tobacco mosaic virus(anti-TMV) activities were isolated from Nicotiana tabacum . Since gene-editing mutants provide a new sample for thediscovery of active metabolites, we focused on the stems ofYN-18–23 (a mutant N. tabacum for gene editing with thealkaloid metabolic pathway cultivated by Yunnan TobaccoCompany), which led to the isolation of four new ( 1–4 )and four known ( 5–8 ) isoindolin-1-ones. To the best of ourknowledge, nicindole C ( 3 ) is the fi rst subclass of isoindolin-1-one bearing a pentacyclic ketone, while nicindole D ( 4 )is the fi rst example of isoindolin-1-one bearing a methylpyridin-2-(1 H )-one moiety. Compounds 1–4 were testedfor their anti-TMV activities, and the results revealed thatcompounds 1 , 3 , and 4 exhibited high anti-TMV activities atconcentrations of 20 μM with inhibition rates of 48.6, 42.8,and 71.5%, respectively. These rates are higher than the inhibitionrate of the positive control (33.2%). The mechanisticstudy of compound 4 , which had the highest anti-TMV activityrevealed that increased potentiation of defense-related enzyme activities and downregulation of expression of theNtHsp70 protein may induce resistance in tobacco againstthe viral pathogen TMV. Molecular docking studies alsorevealed that the isoindolin-1-one substructure is fundamentalfor anti-TMV activity. The methyl-pyridin-2-(1 H )-onemoiety in compound 4 and the 2-oxopropyl groups in compounds1 and 3 at the N -2 position may increase inhibitoryactivities. This study of the structure–activity relationshipis helpful for fi nding new anti-TMV activity inhibitors. Tostudy whether the isoindolin-1-ones have broader antiviralactivities, compounds 1–4 were also tested for their antirotavirusactivities. Compound 4 exhibited high anti-rotavirusactivity with a therapeutic index (TI) value of 20.7. This TI value is close to that of the positive control (20.2).

Anti-tumor Efficacy of a Hepatocellular Carcinoma Vaccine Based on Dendritic Cells Combined with Tumor-derived Autophagosomes in Murine Models

Su, Shu,Zhou, Hao,Xue, Meng,Liu, Jing-Yu,Ding, Lei,Cao, Meng,Zhou, Zhen-Xian,Hu, Hong-Min,Wang, Li-Xin Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.5

The majority of hepatocellular carcinoma (HCC) patients have a poor prognosis with current therapies, and new approaches are urgently needed. We have developed a novel therapeutic cancer vaccine platform based on tumor cell derived autophagosomes (DRibbles) for cancer immunotherapy. We here evaluated the effectiveness of DRibbles-pulsed dendritic cell (DC) immunization to induce anti-tumor immunity in BALB/c mouse HCC and humanized HCC mouse models generated by transplantation of human HCC cells (HepG2) into BALB/c-nu mice. DRibbles were enriched from H22 or BNL cells, BALB/c-derived HCC cell lines, by inducing autophagy and blocking protein degradation. DRibbles-pulsed DC immunization induced a specific T cell response against HCC and resulted in significant inhibition of tumor growth compared to mice treated with DCs alone. Antitumor efficacy of the DCs-DRibbles vaccine was also demonstrated in a humanized HCC mouse model. The results indicated that HCC/DRibbles-pulsed DCs immunotherapy might be useful for suppressing the growth of residual tumors after primary therapy of human HCC.

Improvement of energy storage performance in PbZr0.52Ti0.48O3/PbZrO3 multilayer thin films via regulating PbZrO3 thickness

Yang Fei,Shi Yu Jia,Lin Lin,Chen Jing Yao,Hou Meng Zhe,Yu Ke Xin,Zhang Yi Han,Yuan Zheng,Li Xiao Fang,Hu Yan Chun,Shang Jun,Yin Shao Qian,Wang Xian Wei 한국물리학회 2023 Current Applied Physics Vol.50 No.-

In this work, to prepare the PbZr0.52Ti0.48O3(PZT)/PbZrO3(PZ) multilayer films, PZ films and PZT films were spin-coated on LaNiO3/SiO2/Si substrates in sequence by the sol-gel method, and the PZ films were prepared using PZ precursor solution with different concentrations. After each spin-coating, PZ layer and PZT layer were annealed with rapid thermal annealing (RTA) technique at 650 ◦C and 550 ◦C, respectively. The crystal structures, microstructures and electrical properties of the films with different PZ film thickness were comprehensively investigated. The PZ films with different thickness showed perovskite phase. The PZT films on crystallized PZ films exhibited the coexistence of pyrochlore phase and perovskite phase at the annealing temperature of 550 ◦C. The PZT/PZ multilayer films with 0.2 M PZ precursor solution exhibit typical anti-ferroelectricity with double hysteresis loops, while other multilayer films exhibit nearly linear loops. In addition, the recoverable energy storage density increases with the increase of the film thickness and reaches the maximum value 32.4 J/ cm3 in the PZT/PZ multilayer films with 0.4 M PZ precursor solution. Therefore, the ferroelectric properties of the PZT/PZ multilayer films could be regulated by different PZ film thickness, which effectively further enhances the energy storage performance.

Halomonas alkalitolerans sp. nov., a Novel Moderately Halophilic Bacterium Isolated from Soda Meadow Saline Soil in Daqing, China

Shuang Wang,Qian Yang,Zhi-Hua Liu,Lei Sun,Dan Wei,Jun-Zheng Zhang,Jin-Zhu Song,Yun Wang,Jia Song,Jin-Xia Fan,Xian-Xin Meng,Wei Zhang 한국미생물학회 2011 The journal of microbiology Vol.49 No.1

A moderately halophilic bacterial strain 15-13^T, which was isolated from soda meadow saline soil in Daqing City, Heilongjiang Province, China, was subjected to a polyphasic taxonomic study. The cells of strain 15-13^T were found to be Gram-negative, rod-shaped, and motile. The required growth conditions for strain 15-13^T were: 1-23% NaCl (optimum, 7%), 10-50°C (optimum, 35°C), and pH 7.0-11.0 (optimum, pH 9.5). The predominant cellular fatty acids were C18:1 ω7c (60.48%) and C16:0 (13.96%). The DNA G+C content was 67.6 mol%. Phylogenetic analysis based on 16S rRNA gene sequence comparisons indicated that strain 15-13^T clustered within a branch comprising species of the genus Halomonas. The closest phylogenetic neighbor of strain 15-13^T was Halomonas pantelleriensis DSM 9661^T (98.9% 16S rRNA gene sequence similarity). The level of DNA-DNA relatedness between the novel isolated strain and H. pantelleriensis DSM 9661^T was 33.8%. On the basis of the phenotypic and phylogenetic data, strain 15-13^T represents a novel species of the genus Halomonas, for which the name Halomonas alkalitolerans sp. nov. is proposed. The type strain for this novel species is 15-13^T (=CGMCC 1.9129^T =NBRC 106539^T).