Triptolide induces DNA breaks, activates caspase‑3‑dependent apoptosis and sensitizes B‑cell lymphoma to poly(ADP‑ribose) polymerase 1 and phosphoinositide 3‑kinase inhibitors

Guan,Jiawei; Zhao,Qian; Lv,Jian; Zhang,Zhiwei; Sun,Shijie; Mao,Weifeng

doi:10.3892/ol.2017.6771

Triptolide induces DNA breaks, activates caspase‑3‑dependent apoptosis and sensitizes B‑cell lymphoma to poly(ADP‑ribose) polymerase 1 and phosphoinositide 3‑kinase inhibitors

Authors:
- Jiawei Guan
- Qian Zhao
- Jian Lv
- Zhiwei Zhang
- Shijie Sun
- Weifeng Mao
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Affiliations: Department of Biotechnology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China, Department of Immunology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China
Published online on: August 18, 2017 https://doi.org/10.3892/ol.2017.6771
Pages: 4965-4970

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Abstract

Triptolide is the primary compound isolated from Tripterygium wilfordii, which has been reported to inhibit nucleotide excision repair as well as exhibit anti‑inflammatory and antitumor activities. However, the action of triptolide in DNA breaks remains unknown. The present study investigated the effects of triptolide in the induction of DNA breaks and apoptosis in a murine B‑cell lymphoma cell line, CH12F3. An MTT assay revealed that X‑ray repair cross‑complementing protein 1 (XRCC1)‑/‑ CH12F3 cells were more sensitive to 6 nM triptolide compared with the wild‑type CH12F3 cells, which suggests that low levels of triptolide induce DNA breaks in a manner that is dependent on the XRCC1‑mediated repair pathway. Flow cytometric analysis identified that 50 nM triptolide increased the phospho‑histone H2AX level, demonstrating that triptolide induces double‑strand breaks. Western blot analysis revealed that triptolide up‑regulated Rad51 and nuclear proliferating cell nuclear antigen. Annexin V/propidium iodide staining identified that triptolide promoted apoptosis and western blot analysis confirmed that triptolide activated caspase‑3‑dependent apoptosis. The results of the present study also demonstrated that 5 nM triptolide sensitized CH12F3 lymphoma cells to poly(ADP‑ribose) polymerase 1 and phosphoinositide 3‑kinase inhibitors, suggesting that triptolide may be a potent antitumor drug for sensitizing lymphoma cells to chemotherapeutic agents.

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