Toxicarioside N induces apoptosis in human gastric cancer SGC- 7901 cell by activating the p38MAPK pathway

Huan-ge Zhao,Song-lin Zhou,Ying-ying Lin,Hao Fu Dai,Feng-Ying Huang 대한약학회 2018 Archives of Pharmacal Research Vol.41 No.1

Natural plant compounds with potent proliferationinhibition and apoptosis induction properties havebeen screened as novel anticancer drugs. Toxicarioside N(Tox N) was isolated from the seeds of the tropical plantAntiaris toxicaria in Hainan province, China. To ourknowledge, the effects that Tox N has on the apoptosis ofSGC-7901 cells and its potential mechanism have neverbeen investigated. In this study, we detected the anticanceractivities of Tox N and explored the potential mechanismin the human gastrointestinal cancer cell line SGC-7901. Here, we found that Tox N inhibited SGC-7901 cell growthin a dose- and time-dependent manner and induced apoptosisin cells based on cell morphology and flow cytometryanalyses. Additionally, the SGC-7901 cell treated with ToxN up-regulated the expression level of cleaved caspase-3/9and PARP, increased the Bax/Bcl-2 ratio, and led to therelease of cytochrome c into the cytoplasm. In addition,Tox N treatment led to the phosphorylation of p38MAPK. SB203580, a p38MAPK inhibitor, partially attenuated ToxN induced apoptosis by preventing the activation of caspase-3/9 and PARP. Our results indicated for the first timethat Tox N can induce SGC-7901 cells apoptosis by activatingthe p38MAPK pathway.

Autophagy plays a protective role against apoptosis induced by toxicarioside N via the Akt/mTOR pathway in human gastric cancer SGC-7901 cells

Huan-ge Zhao,Song-lin Zhou,Ying-ying Lin,Hua Wang,Hao Fu Dai,Feng-Ying Huang 대한약학회 2018 Archives of Pharmacal Research Vol.41 No.10

Toxicarioside N (Tox N), a natural product extract from Antiaris toxicaria, has been reported to induce apoptosis in human gastric cancer cells. However, the mechanism and actual role of autophagy in Tox N-induced apoptosis of human gastric cancer cells remains poorly understood. In the current study, we demonstrated that Tox N could induce autophagy by inhibiting the Akt/mTOR signaling pathway in SGC-7901 cells. Moreover, we found that the inhibition of autophagy by 3-methyladenine, an autophagy inhibitor, enhanced Tox N-induced apoptotic cell death. However, the stimulation of autophagy by rapamycin, an autophagy activator, remarkably suppressed Tox N-induced apoptosis, suggesting that autophagy plays a protective role in Tox N-induced apoptosis. Thus, the results from this study suggested that Tox N combination with an autophagy inhibitor might be a promising strategy to enhance the anticancer activity of Tox N for the treatment of human gastric cancer.

Upregulation and biological function of transmembrane protein 119 in osteosarcoma

Zhen-Huan Jiang,Jun Peng,Hui-Lin Yang,Xing-Li Fu,Jin-Zhi Wang,Lei Liu,Jian-Nong Jiang,Yong-Fei Tan,Zhi-Jun Ge 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

Osteosarcoma is suggested to be caused by genetic and molecular alterations that disrupt osteoblast differentiation. Recent studies have reported that transmembrane protein 119 (TMEM119) contributes to osteoblast differentiation and bone development. However, the level of TMEM119 expression and its roles in osteosarcoma have not yet been elucidated. In the present study, TMEM119 mRNA and protein expression was found to be up-regulated in osteosarcoma compared with normal bone cyst tissues. The level of TMEM119 protein expression was strongly associated with tumor size, clinical stage, distant metastasis and overall survival time. Moreover, gene set enrichment analysis (GSEA) of the Gene Expression Omnibus (GEO) GSE42352 dataset revealed TMEM119 expression in osteosarcoma tissues to be positively correlated with cell cycle, apoptosis, metastasis and TGF-β signaling. We then knocked down TMEM119 expression in U2OS and MG63 cells using small interfering RNA, which revealed that downregulation of TMEM119 could inhibit the proliferation of osteosarcoma cells by inducing cell cycle arrest in G0/G1 phase and apoptosis. We also found that TMEM119 knockdown significantly inhibited cell migration and invasion, and decreased the expression of TGF-β pathway-related factors (BMP2, BMP7 and TGF-β). TGF-β application rescued the inhibitory effects of TMEM119 knockdown on osteosarcoma cell migration and invasion. Further in vitro experiments with a TGF-β inhibitor (SB431542) or BMP inhibitor (dorsomorphin) suggested that TMEM119 significantly promotes cell migration and invasion, partly through TGF-β/BMP signaling. In conclusion, our data support the notion that TMEM119 contributes to the proliferation, migration and invasion of osteosarcoma cells, and functions as an oncogene in osteosarcoma.

Penicilazaphilone C, a new antineoplastic and antibacterial azaphilone from the Marine Fungus Penicillium sclerotiorum

Song-lin Zhou,Min Wang,Huan-ge Zhao,Yong-hao Huang,Ying-ying Lin,Guang-hong Tan,Shung-lin Chen 대한약학회 2016 Archives of Pharmacal Research Vol.39 No.12

Two azaphilonidal derivatives [penicilazaphilonesB (1) and C (2)], have been isolated from thefermented products of marine fungus strain Penicilliumsclerotiorum M-22, penicilazaphilones C was a new compound. The compound’s structures were identified by theanalysis of spectroscopic data including 1D and 2D NMRtechniques (1H-NMR, 13C-NMR, COSY, HMQC, andHMBC). Biological evaluation revealed that penicilazaphilonesB and C showed selective cytotoxicity againstmelanoma cells B-16 and human gastric cancer cells SGC-7901 with IC50 values of 0.291, 0.449 and 0.065,0.720 mM, respectively, while exhibiting no significanttoxicity to normal mammary epithelial cells M10 at thesame concentration. Moreover, penicilazaphilones C alsoexhibited strong antibacterial activity against Staphylococcusaureus, Pseudomonas aeruginosa, Klebsiellapneumonia and Escherichia coli with MIC values0.037–0.150 mM, while penicilazaphilones B’s bacteriostaticaction was weaker.

Transcription Profiling of a Revealed the Potential Molecular Mechanism of Governor Vessel Electroacupuncture for Spinal Cord Injury in Rats

Xingru Xiao,Qingwen Deng,Xiang Zeng,Bi-Qin Lai,Yuan-Huan Ma,Ge Li,Yuan-Shan Zeng,Ying Ding 대한척추신경외과학회 2022 Neurospine Vol.19 No.3

Objective: This study aimed to identify differentially expressed genes (DEGs) by transcriptome analysis to elucidate a potential mechanism by which governor vessel electroacupuncture (GV-EA) promotes neuronal survival, axonal regeneration, and functional recovery after complete transection spinal cord injury (SCI). Methods: Sham, control, or GV-EA group adult female Sprague Dawley rats underwent a complete transection SCI protocol. SCI area RNA-seq investigated the DEGs of coding and noncoding RNAs 7 days post-SCI. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were used to classify DEGs functions, to explain a possible molecular mechanism. Immunofluorescence and BBB (Basso, Beattie, and Bresnahan) score were used to verify a GV-EA treatment effect following SCI. Results: GV-EA treatment could regulate the expression of 173 mRNA, 260 lncRNA, and 153 circRNA genes among these DEGs resulted by SCI. GO enrichment analysis showed that the DEGs were most enriched in membrane, actin binding, and regulation of Toll-like receptor signaling pathway. KEGG pathway analysis showed enriched pathways (e.g. , Tolllike receptors, MAPK, Hippo signaling). According to the ceRNA network, miR-144-3p played a regulatory role by interacting with lncRNA and circRNA. GV-EA also promoted the injured spinal cord neuron survival, axonal regeneration, and functional improvement of hind limb locomotion. Conclusion: Results of our RNA-seq suggest that post-SCI GV-EA may regulate characteristic changes in transcriptome gene expression, potential critical genes, and signaling pathways, providing clear directions for further investigation into the mechanism of GV-EA in subacute SCI treatment. Moreover, we found that GV-EA promotes neuronal survival, nerve fiber extension, and motor function recovery in subacute SCI.