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Abstract
Gravitational forces can impose physical stresses on the human body as it functions to maintain homeostasis. It has been reported that astronauts exposed to microgravity experience altered biological functions and many subsequent studies on the effects of microgravity have therefore been conducted. However, the anticancer mechanisms of simulated microgravity remain unclear. We previously showed that the proliferation of human Hodgkin’s lymphoma (HL) cells was inhibited when these cells were cultured in time-averaged simulated microgravity (taSMG). In the present study, we investigated whether taSMG produced an anticancer effect. Exposure of human HL cells to taSMG for 2 days increased their reactive oxygen species (ROS) production and NADPH oxidase family gene expression, while mitochondrial mass, ATPase, ATP synthase, and intracellular ATP levels were decreased. Furthermore, human HL cells exposed to taSMG underwent autophagy via AMPK/Akt/mTOR and MAPK pathway modulation; such autophagy was inhibited by the ROS scavenger N-acetylcysteine (NAC). These results suggest an innovative therapeutic approach to HL that is markedly different from conventional chemotherapy and radiotherapy.
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1 Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea; Biomedical Science Project (BK21PLUS), Seoul National University College of Medicine, Seoul, Republic of Korea
2 Interdisciplinary Program for Bioengineering, Graduate School, Seoul National University, Seoul, Korea
3 Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul, Republic of Korea
4 Biomedical Science Project (BK21PLUS), Seoul National University College of Medicine, Seoul, Republic of Korea
5 Department of Biological Science, Dong-A University, Busan, Republic of Korea
6 Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea; Ischemic/Hypoxic Disease Institute, and Seoul National University College of Medicine, Seoul, Republic of Korea
7 Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul, Republic of Korea; Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea
8 Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea; Biomedical Science Project (BK21PLUS), Seoul National University College of Medicine, Seoul, Republic of Korea; Ischemic/Hypoxic Disease Institute, and Seoul National University College of Medicine, Seoul, Republic of Korea; Neuro-Immune Information Storage Network Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea