Format

Send to

Choose Destination
Toxicol Appl Pharmacol. 2018 Mar 1;342:1-13. doi: 10.1016/j.taap.2018.01.011. Epub 2018 Feb 4.

Triptolide induces mitochondria-mediated apoptosis of Burkitt's lymphoma cell via deacetylation of GSK-3β by increased SIRT3 expression.

Author information

1
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
2
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China. Electronic address: hzhiying@mail.sysu.edu.cn.
3
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China. Electronic address: shenfh3@mail.sysu.edu.cn.

Abstract

Burkitt's lymphoma (BL) is a highly aggressive B-cell non-Hodgkin lymphoma with rapid growth and dissemination propensity. Triptolide (TP), an active component extracted from Chinese herb Tripterygium wilfordii Hook f., has broad-spectrum anti-tumor activities. This study aimed to explore the in vitro and in vivo anti-cancer effects of TP on BL and the potential molecular mechanisms. In this study, the in vitro anti-tumor activity of TP was determined by CCK-8 and flow cytometry assays in Raji, NAMALWA and Daudi cells. The expression of SIRT3, phosphorylation and acetylation of glycogen synthase kinase-3β (GSK-3β) were analyzed by Western blot assay. Moreover, we examined the mitochondrial membrane potential by JC-1 method and measured apoptosis related protein using Western blot assay. BL xenograft model in NOD/SCID mice were established to evaluate the in vivo anti-cancer effect of TP. We discovered that TP inhibited BL cell growth and induced apoptosis in a dose-dependent manner. Loss of SIRT3 provides growth advances for BL cells. However, TP could up-regulate SIRT3 expression, which resulted in suppression of BL cells proliferation. GSK-3β was activated by SIRT3-mediated deacetylation, which subsequently induced mitochondrial translocation and accumulation of Bax and decrease of mitochondrial membrane potential. Anti-tumor studies in vivo showed that TP (0.36 mg/kg) inhibited the growth of BL xenografts in NOD/SCID mice with an inhibitory rate of 73.13%. Our data revealed that TP triggered mitochondrial apoptotic pathway in BL by increasing SIRT3 expression and activating SIRT3/GSK-3β/Bax pathway. This study indicated that TP is a potential anti-cancer Chinese herbal medicine against BL.

KEYWORDS:

Burkitt's lymphoma; GSK-3β; SIRT3; Triptolide; apoptosis

PMID:
29407771
DOI:
10.1016/j.taap.2018.01.011
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center