Induction of Malignant Glioma Cell Death by a Novel Synthesized ?-carboline Derivative TJY-16

論文翻譯標題: 新穎?-?吧?衍生物TJY-16誘導惡性神經膠質瘤死亡機轉之探討
  • 黃 筱杰

學生論文: Master's Thesis


Malignant gliomas are the most lethal primary brain tumors of the central nervous system Although the incidence of brain tumor is lower than lung cancer brain tumor is rarely curable in spite of receiving surgery chemotherapy and radiotherapy The median survival is only 14 6 months Therefore it is important and urgently needed to develop a potential anti-malignant glioma drug The ?-carboline (pyrido[2 3-b]indole) derivatives were abundant in the marine animals Previous studies have focused on their biological activities such as anti-plasmodial anti-virus and anti-tumor We aim to investigate the anti-tumor activity and mechanisms of novel synthesized ?-carboline derivatives TJY against malignant gliomas After screening 6 TJY compounds we found that TJY-16 (6-acetyl-9- (3 4 5-trimethoxybenzyl)-9H-pyrido[2 3-b]indole) had the most powerful anti-glioma effects TJY-16 decreased cell viability of C6 U87 T98G and U251 glioma cell lines in a dose- and time-dependent manner without affecting normal glia cell line SVGP12 Trypan blue exclusion assay further showed the reduction of cell viability was due to both cell growth inhibition and cell death induction after TJY-16 treatment in U87 T98G and U251 glioma cells Flow cytometric analysis indicated that both G2/M phase and sub-G1 phase increased after treatment with TJY-16 Using Hoechst staining of nucleus we found that TJY-16 induced chromatin condensation and DNA fragmentation typical features of apoptosis Western blotting showed the activation of caspase-8 a crucial upstream mediator of extrinsic apoptotic pathway Furthermore JC-1 staining demonstrated that depolarization of mitochondrial membrane potential (ΔΨm) occurred in cells treated with TJY-16 in a time-dependent manner It suggested that both extrinsic and intrinsic apoptotic pathway were involved in TJY-16-induced apoptosis Finally the subcutaneous xenograft model showed that the growth rate of tumor in TJY-16-treated group was slower than control group The body weight of nude mice and H&E staining for organ histology revealed that there was no obvious difference between control and TJY-16-treated group It indicated that TJY-16 effectively inhibited glioma in vitro and in vivo In summary we suggested that TJY-16 seemed to be a promising agent in the treatment of malignant gliomas
獎項日期2014 七月 30
監督員Po-Wu Gean (Supervisor)