Pharmacological Ascorbate Elicits Anti-Cancer Activities against Non-Small Cell Lung Cancer through Hydrogen-Peroxide-Induced-DNA-Damage
Non-small cell lung cancer (NSCLC) poses a significant global health burden with unsatisfactory survival rates, despite advancements in diagnostic and therapeutic modalities. Novel therapeutic approaches are urgently required to improve patient outcomes. Pharmacological ascorbate (P-AscH<sup>−...
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| Format: | Article |
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MDPI AG
2023-09-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/9/1775 |
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| author | Kittipong Sanookpan Naphat Chantaravisoot Nuttiya Kalpongnukul Chatchapon Chuenjit Onsurang Wattanathamsan Sara Shoaib Pithi Chanvorachote Visarut Buranasudja |
| author_facet | Kittipong Sanookpan Naphat Chantaravisoot Nuttiya Kalpongnukul Chatchapon Chuenjit Onsurang Wattanathamsan Sara Shoaib Pithi Chanvorachote Visarut Buranasudja |
| author_sort | Kittipong Sanookpan |
| collection | DOAJ |
| description | Non-small cell lung cancer (NSCLC) poses a significant global health burden with unsatisfactory survival rates, despite advancements in diagnostic and therapeutic modalities. Novel therapeutic approaches are urgently required to improve patient outcomes. Pharmacological ascorbate (P-AscH<sup>−</sup>; ascorbate at millimolar concentration in plasma) emerged as a potential candidate for cancer therapy for recent decades. In this present study, we explore the anti-cancer effects of P-AscH<sup>−</sup> on NSCLC and elucidate its underlying mechanisms. P-AscH<sup>−</sup> treatment induces formation of cellular oxidative distress; disrupts cellular bioenergetics; and leads to induction of apoptotic cell death and ultimately reduction in clonogenic survival. Remarkably, DNA and DNA damage response machineries are identified as vulnerable targets for P-AscH<sup>−</sup> in NSCLC therapy. Treatments with P-AscH<sup>−</sup> increase the formation of DNA damage and replication stress markers while inducing mislocalization of DNA repair machineries. The cytotoxic and genotoxic effects of P-AscH<sup>−</sup> on NSCLC were reversed by co-treatment with catalase, highlighting the roles of extracellular hydrogen peroxide in anti-cancer activities of P-AscH<sup>−</sup>. The data from this current research advance our understanding of P-AscH<sup>−</sup> in cancer treatment and support its potential clinical use as a therapeutic option for NSCLC therapy. |
| first_indexed | 2024-03-10T23:05:23Z |
| format | Article |
| id | doaj.art-55ca4bda1546477cb501b23c98f5bcae |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T23:05:23Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-55ca4bda1546477cb501b23c98f5bcae2023-11-19T09:20:18ZengMDPI AGAntioxidants2076-39212023-09-01129177510.3390/antiox12091775Pharmacological Ascorbate Elicits Anti-Cancer Activities against Non-Small Cell Lung Cancer through Hydrogen-Peroxide-Induced-DNA-DamageKittipong Sanookpan0Naphat Chantaravisoot1Nuttiya Kalpongnukul2Chatchapon Chuenjit3Onsurang Wattanathamsan4Sara Shoaib5Pithi Chanvorachote6Visarut Buranasudja7Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandCenter of Excellence in Systems Biology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, ThailandNon-small cell lung cancer (NSCLC) poses a significant global health burden with unsatisfactory survival rates, despite advancements in diagnostic and therapeutic modalities. Novel therapeutic approaches are urgently required to improve patient outcomes. Pharmacological ascorbate (P-AscH<sup>−</sup>; ascorbate at millimolar concentration in plasma) emerged as a potential candidate for cancer therapy for recent decades. In this present study, we explore the anti-cancer effects of P-AscH<sup>−</sup> on NSCLC and elucidate its underlying mechanisms. P-AscH<sup>−</sup> treatment induces formation of cellular oxidative distress; disrupts cellular bioenergetics; and leads to induction of apoptotic cell death and ultimately reduction in clonogenic survival. Remarkably, DNA and DNA damage response machineries are identified as vulnerable targets for P-AscH<sup>−</sup> in NSCLC therapy. Treatments with P-AscH<sup>−</sup> increase the formation of DNA damage and replication stress markers while inducing mislocalization of DNA repair machineries. The cytotoxic and genotoxic effects of P-AscH<sup>−</sup> on NSCLC were reversed by co-treatment with catalase, highlighting the roles of extracellular hydrogen peroxide in anti-cancer activities of P-AscH<sup>−</sup>. The data from this current research advance our understanding of P-AscH<sup>−</sup> in cancer treatment and support its potential clinical use as a therapeutic option for NSCLC therapy.https://www.mdpi.com/2076-3921/12/9/1775pharmacological ascorbateanti-cancernon-small cell lung cancerDNA damagepro-oxidantadjuvant |
| spellingShingle | Kittipong Sanookpan Naphat Chantaravisoot Nuttiya Kalpongnukul Chatchapon Chuenjit Onsurang Wattanathamsan Sara Shoaib Pithi Chanvorachote Visarut Buranasudja Pharmacological Ascorbate Elicits Anti-Cancer Activities against Non-Small Cell Lung Cancer through Hydrogen-Peroxide-Induced-DNA-Damage Antioxidants pharmacological ascorbate anti-cancer non-small cell lung cancer DNA damage pro-oxidant adjuvant |
| title | Pharmacological Ascorbate Elicits Anti-Cancer Activities against Non-Small Cell Lung Cancer through Hydrogen-Peroxide-Induced-DNA-Damage |
| title_full | Pharmacological Ascorbate Elicits Anti-Cancer Activities against Non-Small Cell Lung Cancer through Hydrogen-Peroxide-Induced-DNA-Damage |
| title_fullStr | Pharmacological Ascorbate Elicits Anti-Cancer Activities against Non-Small Cell Lung Cancer through Hydrogen-Peroxide-Induced-DNA-Damage |
| title_full_unstemmed | Pharmacological Ascorbate Elicits Anti-Cancer Activities against Non-Small Cell Lung Cancer through Hydrogen-Peroxide-Induced-DNA-Damage |
| title_short | Pharmacological Ascorbate Elicits Anti-Cancer Activities against Non-Small Cell Lung Cancer through Hydrogen-Peroxide-Induced-DNA-Damage |
| title_sort | pharmacological ascorbate elicits anti cancer activities against non small cell lung cancer through hydrogen peroxide induced dna damage |
| topic | pharmacological ascorbate anti-cancer non-small cell lung cancer DNA damage pro-oxidant adjuvant |
| url | https://www.mdpi.com/2076-3921/12/9/1775 |
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