Heavy water (D 2 O) induces autophagy-dependent apoptotic cell death in non-small cell lung cancer A549 cells by generating reactive oxygen species (ROS) upon microtubule disruption.

Autor: Das A; Department of Biotechnology and Dr. B.C. Guha Centre for Genetic Engineering and Biotechnology, University of Calcutta, Kolkata, West Bengal 700019, India; Department of Biochemistry, Royal School of Biosciences, The Assam Royal Global University, Assam 781035, India. Electronic address: adas5@rgu.ac., Chakrabarty S; Department of Biotechnology and Dr. B.C. Guha Centre for Genetic Engineering and Biotechnology, University of Calcutta, Kolkata, West Bengal 700019, India; Department of Microbiology, M.U.C. Women's College, Burdwan, West Bengal 713104, India., Nag D; Department of Biotechnology and Dr. B.C. Guha Centre for Genetic Engineering and Biotechnology, University of Calcutta, Kolkata, West Bengal 700019, India., Paul S; Department of Biotechnology and Dr. B.C. Guha Centre for Genetic Engineering and Biotechnology, University of Calcutta, Kolkata, West Bengal 700019, India; Department of Biotechnology, School of Life Sciences, Swami Vivekananda University, Barrackpore, West Bengal 700121, India., Ganguli A; Department of Microbiology, Techno India University, West Bengal 700091, India., Chakrabarti G; Department of Biotechnology and Dr. B.C. Guha Centre for Genetic Engineering and Biotechnology, University of Calcutta, Kolkata, West Bengal 700019, India. Electronic address: gcbcg@caluniv.ac.in.
Jazyk: angličtina
Zdroj: Toxicology in vitro : an international journal published in association with BIBRA [Toxicol In Vitro] 2023 Dec; Vol. 93, pp. 105703. Date of Electronic Publication: 2023 Sep 24.
DOI: 10.1016/j.tiv.2023.105703
Abstrakt: Objective: Deuterium oxide (D 2 O) or heavy water is known to have diverse biological activities and have a few therapeutic applications due to its limited toxicity to human subjects. In the present study, we investigated the mechanism of D 2 O-induced cytotoxicity in non-small cell lung cancer A549 cells.
Results: We found that D 2 O-treatment resulted in cytotoxicity, cell cycle arrest, and apoptosis in A549 cells in a dose-dependent fashion. In contrast, limited cytotoxicity was observed in lung fibroblasts WI38 cells. Moreover, D 2 O-treatment resulted in the disruption of the cellular microtubule network, accompanied by the generation of ROS. On further investigation, we observed that the intracellular ROS triggered autophagic responses in D 2 O-treated cells, leading to apoptosis by inhibiting the oncogenic PI3K/ Akt/ mTOR signaling. D 2 O-treatment was also found to enhance the efficacy of paclitaxel in A549 cells.
Significance: D 2 O induces autophagy-dependent apoptosis in A549 cells via ROS generation upon microtubule depolymerization and inhibition of PI3K/ Akt/ mTOR signaling. It augments the efficacy of other microtubule-targeting anticancer drug taxol, which indicates the potential therapeutic importance of D 2 O as an anticancer agent either alone or in combination with other chemotherapeutic drugs.
Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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