High dose of ascorbic acid induces cell death in mesothelioma cells

Our plain-English summary of High dose of ascorbic acid induces cell death in mesothelioma cells, by Y. Takemura, M. Satoh, K. Satoh, et al (Biochemical and Biophysical Research Communications, 2010).

The study

• Authors: Y. Takemura, M. Satoh, K. Satoh, H. Hamada, Y. Sekido, S. Kubota
• Journal: Biochemical and Biophysical Research Communications
• Published: 2010;394(2):249-53
• Cited by: 76 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma is an asbestos-related fatal disease with no effective cure. Recently, high dose of ascorbate in cancer treatment has been reexamined. We studied whether high dose of ascorbic acid induced cell death of four human mesothelioma cell lines. High dose of ascorbic acid induced cell death of all mesothelioma cell lines in a dose-dependent manner. We further clarified the cell killing mechanism that ascorbic acid induced reactive oxygen species and impaired mitochondrial membrane potential. In vivo experiment, intravenous administration of ascorbic acid significantly decreased the growth rate of mesothelioma tumor inoculated in mice. These data suggest that ascorbic acid may have benefits for patients with mesothelioma.

2010 Elsevier Inc. All rights reserved.

In plain English

This was a laboratory study, not a study of people or of asbestos exposure. The authors tested high doses of ascorbic acid (vitamin C) on four human mesothelioma cell lines and on mesothelioma tumors grown in mice. After 24 hours, ascorbic acid reduced the survival of all four cell lines, more strongly at higher doses. The concentration that cut survival by half ranged from 80 µM (EHMES-1) to 640 µM (EHMES-10). In one-hour tests at 10 mM, two cell lines did not survive and two did. In EHMES-10 cells, ascorbic acid impaired the membrane potential of the mitochondria (the cells' energy-producing parts) more as the dose rose, and two antioxidant substances, catalase and tempol, completely prevented the cell death. In mice, a single injection into a vein left tumors significantly smaller than in control mice on day 20. By day 34 there were no significant differences in tumor size. The authors concluded that high-dose ascorbic acid induced cell death in all four mesothelioma cell lines tested. They said repeated injections appear necessary and that further investigation is needed before clinical use.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory experiment on human mesothelioma cell lines (in vitro), plus an animal experiment in mice carrying human mesothelioma tumors (xenograft)
• Who was studied: Four human mesothelioma cell lines (ACC-MESO 1, Y-MESO 8A, EHMES-10, EHMES-1). EHMES-10 cells were also implanted under the skin of male SCID mice aged 6 to 7 weeks. The number of mice is not stated.
• Exposure: Ascorbic acid (vitamin C), not asbestos. Cells received 50 to 1000 µM for 24 hours, or 1, 10 and 100 mM for 1 hour. Mice received a single intravenous tail-vein injection of 50 µl of 0.1 M or 1 M ascorbic acid, compared with PBS (control). For comparison, EHMES-10 cells were also tested with the cancer drug cisplatin.
• Main results:
  • After 24 hours of treatment, ascorbic acid reduced survival of all four cell lines in a dose-dependent manner.
  • Concentrations that decreased cell survival by 50% (EC50) were 120 µM (ACC-MESO), 610 µM (Y-MESO), 80 µM (EHMES-1) and 640 µM (EHMES-10).
  • With 1-hour treatment, ACC-MESO and EHMES-1 cells were not viable at 10 mM, while Y-MESO and EHMES-10 cells remained viable at 10 mM.
  • In EHMES-10 cells, ascorbic acid impaired mitochondrial membrane potential in a dose-dependent manner.
  • In EHMES-10 cells, catalase completely prevented ascorbic acid-induced cell death, and tempol was also completely protective.
  • In mice with EHMES-10 tumors, tumor growth in both ascorbic acid groups (0.1 M and 1 M) was significantly decreased on day 20 compared with the PBS control group. On day 34 there were no significant differences in tumor size between any groups.
• The authors' conclusion: The authors concluded that high-dose ascorbic acid induced cell death in all the mesothelioma cells tested, and that further investigations are needed for clinical application in mesothelioma.
• Limitations the authors state:
  • A single injection did not keep tumors significantly smaller by day 34. The authors stated that several injections would be needed for continued inhibition of tumor growth.
  • The mesothelioma cell lines differed in their sensitivity to ascorbic acid.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Malignant Mesothelioma, Reactive Oxygen Species (ROS).

Related studies

• Iron mobilization from asbestos by chelators and ascorbic acid — L.G. Lund, A.E. Aust (1990)
• Ascorbic acid modifies the surface of asbestos: possible implications in the molecular mechanisms of toxicity — G. Martra, M. Tomatis, et al. (2003)
• Protective role of ascorbic acid against asbestos induced toxicity in rat lung: in vitro study — S.G. Khan, S. Ali, et al. (1990)
• Ascorbic acid inhibits the squamous metaplasia that results from treatment of tracheal explants with asbestos or benzo[a]pyrene-coated asbestos — G. Holtz, E. Bresnick (1988)
• The levels of HDAC1 and thioredoxin1 are related to the death of mesothelioma cells by suberoylanilide hydroxamic acid — B.R. You, W.H. Park (2016)
• Zebularine exerts its antiproliferative activity through S phase delay and cell death in human malignant mesothelioma cells — Y. Takemura, M. Satoh, et al. (2018)

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