Sulfasalazine Sensitizes Polyhematoporphyrin-Mediated Photodynamic Therapy in Cholangiocarcinoma by Targeting xCT
Cholangiocarcinoma (CCA), which is highly malignant, shows a relatively poor prognosis, due to the insensitivity of the tumour to chemotherapy and radiotherapy. Photodynamic therapy (PDT) has become a promising palliative therapeutic option for patients with unresectable cholangiocarcinoma (CCA), wh...
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| Format: | Article |
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Frontiers Media S.A.
2021-08-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.723488/full |
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| author | Yan-Wen Zheng Xiong-Ying Miao Li Xiong Bo Chen Fan-Hua Kong Jiang-Jiao Zhou Zhong-Tao Liu Yu Wen Zi-Jian Zhang Heng Zou |
| author_facet | Yan-Wen Zheng Xiong-Ying Miao Li Xiong Bo Chen Fan-Hua Kong Jiang-Jiao Zhou Zhong-Tao Liu Yu Wen Zi-Jian Zhang Heng Zou |
| author_sort | Yan-Wen Zheng |
| collection | DOAJ |
| description | Cholangiocarcinoma (CCA), which is highly malignant, shows a relatively poor prognosis, due to the insensitivity of the tumour to chemotherapy and radiotherapy. Photodynamic therapy (PDT) has become a promising palliative therapeutic option for patients with unresectable cholangiocarcinoma (CCA), while the functional amount of ROS is limited by intracellular redox systemen. Sulfasalazine (SASP), a well-known anti-inflammatory agent, which also acts as an inhibitor of the amino acid transport system xc (xCT), decreases the intracellular glutathione (GSH) level, thus weakening the antioxidant defence of the cell by inhibition of the antiporter. However, the combination of SASP and PDT remains unexplored. We have reported that polyhematoporphyrin (PHP)-mediated PDT inhibits the cell viability of CCA cells and organoids. Furthermore, in PHP-enriched HCCC-9810 and TFK-1CCA cells, SASP enhances the sensitivity to PHP-mediated PDT through a GSH-dependent mechanism. We found that PHP-PDT can up-regulate xCT expression to promote cells against overloaded ROS, while SASP reduces GSH levels. After the combination of SASP and PHP-PDT, cell viability and GSH levels were significantly inhibited. xCT was also observed to be inhibited by SASP in human organoid samples. Our findings suggest that, in combination with PDT, SASP has potential as a promising approach against CCA. |
| first_indexed | 2024-12-19T15:46:32Z |
| format | Article |
| id | doaj.art-993679abe4d1403d979ec9ea804af36b |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-19T15:46:32Z |
| publishDate | 2021-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-993679abe4d1403d979ec9ea804af36b2022-12-21T20:15:20ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-08-011210.3389/fphar.2021.723488723488Sulfasalazine Sensitizes Polyhematoporphyrin-Mediated Photodynamic Therapy in Cholangiocarcinoma by Targeting xCTYan-Wen ZhengXiong-Ying MiaoLi XiongBo ChenFan-Hua KongJiang-Jiao ZhouZhong-Tao LiuYu WenZi-Jian ZhangHeng ZouCholangiocarcinoma (CCA), which is highly malignant, shows a relatively poor prognosis, due to the insensitivity of the tumour to chemotherapy and radiotherapy. Photodynamic therapy (PDT) has become a promising palliative therapeutic option for patients with unresectable cholangiocarcinoma (CCA), while the functional amount of ROS is limited by intracellular redox systemen. Sulfasalazine (SASP), a well-known anti-inflammatory agent, which also acts as an inhibitor of the amino acid transport system xc (xCT), decreases the intracellular glutathione (GSH) level, thus weakening the antioxidant defence of the cell by inhibition of the antiporter. However, the combination of SASP and PDT remains unexplored. We have reported that polyhematoporphyrin (PHP)-mediated PDT inhibits the cell viability of CCA cells and organoids. Furthermore, in PHP-enriched HCCC-9810 and TFK-1CCA cells, SASP enhances the sensitivity to PHP-mediated PDT through a GSH-dependent mechanism. We found that PHP-PDT can up-regulate xCT expression to promote cells against overloaded ROS, while SASP reduces GSH levels. After the combination of SASP and PHP-PDT, cell viability and GSH levels were significantly inhibited. xCT was also observed to be inhibited by SASP in human organoid samples. Our findings suggest that, in combination with PDT, SASP has potential as a promising approach against CCA.https://www.frontiersin.org/articles/10.3389/fphar.2021.723488/fullcholangiocarcinomaphotodynamic therapysulfasalazinesolute carrier family 7 member 11polyhematoporphyrin |
| spellingShingle | Yan-Wen Zheng Xiong-Ying Miao Li Xiong Bo Chen Fan-Hua Kong Jiang-Jiao Zhou Zhong-Tao Liu Yu Wen Zi-Jian Zhang Heng Zou Sulfasalazine Sensitizes Polyhematoporphyrin-Mediated Photodynamic Therapy in Cholangiocarcinoma by Targeting xCT Frontiers in Pharmacology cholangiocarcinoma photodynamic therapy sulfasalazine solute carrier family 7 member 11 polyhematoporphyrin |
| title | Sulfasalazine Sensitizes Polyhematoporphyrin-Mediated Photodynamic Therapy in Cholangiocarcinoma by Targeting xCT |
| title_full | Sulfasalazine Sensitizes Polyhematoporphyrin-Mediated Photodynamic Therapy in Cholangiocarcinoma by Targeting xCT |
| title_fullStr | Sulfasalazine Sensitizes Polyhematoporphyrin-Mediated Photodynamic Therapy in Cholangiocarcinoma by Targeting xCT |
| title_full_unstemmed | Sulfasalazine Sensitizes Polyhematoporphyrin-Mediated Photodynamic Therapy in Cholangiocarcinoma by Targeting xCT |
| title_short | Sulfasalazine Sensitizes Polyhematoporphyrin-Mediated Photodynamic Therapy in Cholangiocarcinoma by Targeting xCT |
| title_sort | sulfasalazine sensitizes polyhematoporphyrin mediated photodynamic therapy in cholangiocarcinoma by targeting xct |
| topic | cholangiocarcinoma photodynamic therapy sulfasalazine solute carrier family 7 member 11 polyhematoporphyrin |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.723488/full |
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