α-Carboline derivative TJY-16 inhibits tumor growth by inducing G2/M cell cycle arrest in glioma cells

Journal of Biomedical Science
Hsiao-Chieh HuangPo-Wu Gean

Abstract

Glioblastoma multiforme (GBM) is the most lethal primary brain tumors which remains difficult to cure despite advances in surgery, radiotherapy and chemotherapy. Therefore, the development of new drug is urgently needed. α-carboline derivatives were usually isolated from marine animals such as Britannia marine tunicate Dendrodoa grossularia and Indonesian ascidian Polycarpa aurata. In this study, we have synthesized several α-carboline compounds and examined their anti-glioma activities. We report that among α-carboline derivatives TJY-16 (6-acetyl-9-(3,4,5-trimethoxybenzyl)-9H-pyrido[2,3-b] indole) is the most potent α-carboline analog to induce glioma cell death with IC50 value of around 50 nM. TJY-16 decreased cell viability of glioma cells in a concentration- and time-dependent manner. Trypan blue exclusion assay showed that the reduction of cell viability was due to both cell growth inhibition and cell death. Flow cytometric analysis showed that TJY-16 induced G2/M cell cycle arrest followed by induction of sub-G1 phase. Hoechst staining detected the apoptotic features such as nuclear shrinkage and DNA condensation. Western blot analysis showed the increased level of cleaved caspase-3. The activation of caspase-8 and depol...Continue Reading

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Citations

Jun 18, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Yuanyuan TangYun Liu
Aug 28, 2021·Biomedicines·Rodion KhotimchenkoYuri Khotimchenko

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Methods Mentioned

BETA
xenograft
flow cytometry

Software Mentioned

WinMDI

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