Enhancement of oxaliplatin sensitivity in human colorectal cancer by hypericin mediated photodynamic therapy via ROS-related mechanism. (February 2016)

• Record Type: Journal Article
• Authors: Lin, Shengchao; Lei, Kecheng; Du, Wenpei; Yang, Liyan; Shi, Haiyang; Gao, Yuwei; Yin, Peihao; Liang, Xin; Liu, Jianwen
• Is Part Of: International journal of biochemistry & cell biology. Volume 71(2016:Feb.)
• Page Start: 24
• Page End: 34
• Publication Date: 2016-02
• Subjects: Photodynamic therapy (PDT) -- Hypericin -- Oxaliplatin -- Nucleotide excision repair (NER) -- Glutathione -- Glutathione S-transferase (GST); Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2015.12.003
• Languages: English
• ISSNs: 1357-2725

Abstract

Graphical abstract: Highlights: HY-PDT potentiated the antitumor activity of oxaliplatin. HY-PDT down-regulates MRP2 level and increased intracellular Pt accumulation. HY-PDT adversely affected GSH-related detoxification and NER-mediated DNA repair. Abstract: The resistance to oxaliplatin (L-OHP) is a major obstacle to ideal therapeutic outcomes in colorectal cancer. Photodynamic therapy (PDT) induces tumor damage through photosensitizer-mediated oxidative cytotoxicity. Hypericin is a well-studied photosensitizer. In this study, we explored the role of hypericin-mediated PDT (HY-PDT) in sensitizing human colorectal cancer cells towards L-OHP. Pre-treatment with HY-PDT enhanced the anti-tumor activity of L-OHP via decreasing drug efflux and increasing platinum accumulation. Further research showed that HY-PDT-mediated resensitization of resistance cells towards L-OHP was dependent on regulation of MRP-2, instead of p-gp. HY-PDT was also found to inhibit intracellular glutathione (GSH) and Glutathione S-transferase (GST), suggesting the involvement of GSH-related detoxification in the sensitization effect. Additionally, enhanced DNA double-strand breaks (DSBs) was observed following HY-PDT/L-OHP combined treatment. HY-PDT lowered the removing rate of platinum from DNA and down-regulated the expression of ERCC1 and XPF, two critical enzymes involved in nucleotide excision repair (NER) pathway. GSH monoethyl ester (GSH-EE) antagonized HY-PDT-induced ROS and repressed sensitization to platinum. Taken together, HY-PDT mediated sensitization of L-OHP in human colorectal cancer is mediated by ROS, whose mechanism involves affecting drug efflux, GSH-related detoxification and NER-mediated DNA repair.