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- Title
Pharmacological Ascorbate Elicits Anti-Cancer Activities against Non-Small Cell Lung Cancer through Hydrogen-Peroxide-Induced-DNA-Damage.
- Authors
Sanookpan, Kittipong; Chantaravisoot, Naphat; Kalpongnukul, Nuttiya; Chuenjit, Chatchapon; Wattanathamsan, Onsurang; Shoaib, Sara; Chanvorachote, Pithi; Buranasudja, Visarut
- Abstract
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−; 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− on NSCLC and elucidate its underlying mechanisms. P-AscH− 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− in NSCLC therapy. Treatments with P-AscH− 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− on NSCLC were reversed by co-treatment with catalase, highlighting the roles of extracellular hydrogen peroxide in anti-cancer activities of P-AscH−. The data from this current research advance our understanding of P-AscH− in cancer treatment and support its potential clinical use as a therapeutic option for NSCLC therapy.
- Subjects
NON-small-cell lung carcinoma; ANTINEOPLASTIC agents; DNA repair; DNA replication; THERAPEUTICS; DNA damage
- Publication
Antioxidants, 2023, Vol 12, Issue 9, p1775
- ISSN
2076-3921
- Publication type
Article
- DOI
10.3390/antiox12091775