Hypericin-mediated photodynamic therapy enhances gemcitabine induced Capan-2 cell apoptosis via inhibiting NADPH level

Author:

Sun Liyun1ORCID,Shang Huoli1,Wu Yuzhen1,Xin Xiujuan1

Affiliation:

1. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China

Abstract

Abstract Objectives The combination of gemcitabine (Gem) and hypericin (HY) enhances the apoptosis of Capan-2 cells, providing a promising option for the treatment of pancreatic cancer. Our study further explored the cytotoxic mechanism of HY combined with chemotherapy drugs on pancreatic cancer. Methods The proliferation rate of the cells assayed with the MTT method. The ROS (reactive oxygen species) levels of each treatment were evaluated by DCFH-DA oxidisation methods. The activity of glutathione reductase and the levels of reduced glutathione (GSH) and oxidised glutathione (GSSG) were assessed using assay kits. The expression levels of apoptosis-related proteins were analysed by western blotting. Key findings The activity of glucose-6-phosphate dehydrogenase (G6PDH), a key enzyme of the pentose phosphate pathway, significantly decreased in Gem + HY groups, however, the ROS level enhanced accompanying with GSH depleting, mitochondrial membrane depolarisation and cytochrome C release. Gem + HY inhibits the expression of Bcl-2 but stimulates Bax level, triggering caspase activation and PARP cleavage and thus promoted apoptosis of Capan-2 cells. Conclusions We demonstrated that Gem combined HY-PDT could inhibit the proliferation of Capan-2 cells and induce cell apoptosis. HY-PDT combined with Gem had a great potential on pancreatic cancer treatment clinically.

Funder

The National Natural Science Fund

Beijing Technology and Business

Technology and China Scholarship Council

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

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