Polydatin enhances oxaliplatin-induced cell death by activating NOX5-ROS-mediated DNA damage and ER stress in colon cancer cells
BackgroundPolydatin (3,4′,5-trihydroxy-3-β-d-glucopyranoside, PD) is known for its antioxidant and anti-inflammatory properties. Oxaliplatin (OXA)-based chemotherapy is the first-line treatment for metastatic and recurrent colorectal cancer (CRC). However, the lack of selectivity for normal cells of...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1532695/full |
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| author | Qi Zhao Qi Zhao Qi Zhao Yan Zhang Yan Zhang Jieyu Liu Peipei Chen Annabeth Onga Namki Cho Ri Cui Chenguo Zheng |
| author_facet | Qi Zhao Qi Zhao Qi Zhao Yan Zhang Yan Zhang Jieyu Liu Peipei Chen Annabeth Onga Namki Cho Ri Cui Chenguo Zheng |
| author_sort | Qi Zhao |
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| description | BackgroundPolydatin (3,4′,5-trihydroxy-3-β-d-glucopyranoside, PD) is known for its antioxidant and anti-inflammatory properties. Oxaliplatin (OXA)-based chemotherapy is the first-line treatment for metastatic and recurrent colorectal cancer (CRC). However, the lack of selectivity for normal cells often results in side effects. Consequently, the search for anti-cancer components with high efficacy and low cytotoxicity has become a significant focus in recent years.MethodsThe anti-tumor effects of PD, OXA or their combination were assessed by cell viability, colony formation, and wound-healing assays. Reactive oxygen species (ROS) generation was measured by flow cytometry and DNA damage was assessed by immunofluorescence assay. The relative gene and protein expressions were analyzed by quantitative real time-PCR (qRT-PCR) and Western blot assays. Molecular docking analysis predicted the interaction between PD and potential targets.ResultsWe found that PD exerted anti-CRC activity by promoting Nicotinamide Adenine Dinucleotide Phosphate (NADPH) oxidase 5 (NOX5)-mediated ROS production, activating the endoplasmic reticulum (ER) stress, and inducing DNA damage. Knocking down NOX5 attenuated the inhibition of proliferation and colony forming ability induced by PD in colon cancer cells and reversed the expression of C/EBP-homologous protein (CHOP) and activating transcription factor 4 (ATF4) proteins. In addition, combination of PD and OXA synergistically exerted anti-CRC activities by promoting DNA damage and activating ER stress signaling pathway.ConclusionThe combination of PD and OXA could be an effective treatment strategy for certain patients with CRC. |
| format | Article |
| id | doaj-art-7f5bd729f1eb4c9488c22ffce0cd8d1f |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-7f5bd729f1eb4c9488c22ffce0cd8d1f2025-01-09T06:11:11ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011510.3389/fphar.2024.15326951532695Polydatin enhances oxaliplatin-induced cell death by activating NOX5-ROS-mediated DNA damage and ER stress in colon cancer cellsQi Zhao0Qi Zhao1Qi Zhao2Yan Zhang3Yan Zhang4Jieyu Liu5Peipei Chen6Annabeth Onga7Namki Cho8Ri Cui9Chenguo Zheng10The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaCancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, ChinaCollege of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, Republic of KoreaThe Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaCancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, ChinaThe Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaCancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, ChinaCancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, ChinaCollege of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, Republic of KoreaCancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, ChinaThe Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaBackgroundPolydatin (3,4′,5-trihydroxy-3-β-d-glucopyranoside, PD) is known for its antioxidant and anti-inflammatory properties. Oxaliplatin (OXA)-based chemotherapy is the first-line treatment for metastatic and recurrent colorectal cancer (CRC). However, the lack of selectivity for normal cells often results in side effects. Consequently, the search for anti-cancer components with high efficacy and low cytotoxicity has become a significant focus in recent years.MethodsThe anti-tumor effects of PD, OXA or their combination were assessed by cell viability, colony formation, and wound-healing assays. Reactive oxygen species (ROS) generation was measured by flow cytometry and DNA damage was assessed by immunofluorescence assay. The relative gene and protein expressions were analyzed by quantitative real time-PCR (qRT-PCR) and Western blot assays. Molecular docking analysis predicted the interaction between PD and potential targets.ResultsWe found that PD exerted anti-CRC activity by promoting Nicotinamide Adenine Dinucleotide Phosphate (NADPH) oxidase 5 (NOX5)-mediated ROS production, activating the endoplasmic reticulum (ER) stress, and inducing DNA damage. Knocking down NOX5 attenuated the inhibition of proliferation and colony forming ability induced by PD in colon cancer cells and reversed the expression of C/EBP-homologous protein (CHOP) and activating transcription factor 4 (ATF4) proteins. In addition, combination of PD and OXA synergistically exerted anti-CRC activities by promoting DNA damage and activating ER stress signaling pathway.ConclusionThe combination of PD and OXA could be an effective treatment strategy for certain patients with CRC.https://www.frontiersin.org/articles/10.3389/fphar.2024.1532695/fullcolorectal cancerpolydatinoxaliplatinROSNAPDH oxidase 5DNA damage |
| spellingShingle | Qi Zhao Qi Zhao Qi Zhao Yan Zhang Yan Zhang Jieyu Liu Peipei Chen Annabeth Onga Namki Cho Ri Cui Chenguo Zheng Polydatin enhances oxaliplatin-induced cell death by activating NOX5-ROS-mediated DNA damage and ER stress in colon cancer cells Frontiers in Pharmacology colorectal cancer polydatin oxaliplatin ROS NAPDH oxidase 5 DNA damage |
| title | Polydatin enhances oxaliplatin-induced cell death by activating NOX5-ROS-mediated DNA damage and ER stress in colon cancer cells |
| title_full | Polydatin enhances oxaliplatin-induced cell death by activating NOX5-ROS-mediated DNA damage and ER stress in colon cancer cells |
| title_fullStr | Polydatin enhances oxaliplatin-induced cell death by activating NOX5-ROS-mediated DNA damage and ER stress in colon cancer cells |
| title_full_unstemmed | Polydatin enhances oxaliplatin-induced cell death by activating NOX5-ROS-mediated DNA damage and ER stress in colon cancer cells |
| title_short | Polydatin enhances oxaliplatin-induced cell death by activating NOX5-ROS-mediated DNA damage and ER stress in colon cancer cells |
| title_sort | polydatin enhances oxaliplatin induced cell death by activating nox5 ros mediated dna damage and er stress in colon cancer cells |
| topic | colorectal cancer polydatin oxaliplatin ROS NAPDH oxidase 5 DNA damage |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1532695/full |
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