Open Access

Hypochlorous acid selectively promotes toxicity and the expression of danger signals in human abdominal cancer cells

  • Authors:
    • Eric Freund
    • Lea Miebach
    • Matthias B. Stope
    • Sander Bekeschus
  • View Affiliations

  • Published online on: March 22, 2021     https://doi.org/10.3892/or.2021.8022
  • Article Number: 71
  • Copyright: © Freund et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Tumors of the abdominal cavity, such as colorectal, pancreatic and ovarian cancer, frequently metastasize into the peritoneum. Large numbers of metastatic nodules hinder curative surgical resection, necessitating lavage with hyperthermic intraperitoneal chemotherapy (HIPEC). However, HIPEC not only causes severe side effects but also has limited therapeutic efficacy in various instances. At the same time, the age of immunotherapies such as biological agents, checkpoint‑ inhibitors or immune‑cell therapies, increasingly emphasizes the critical role of anticancer immunity in targeting malignancies. The present study investigated the ability of three types of long‑lived reactive species (oxidants) to inactivate cancer cells and potentially complement current HIPEC regimens, as well as to increase tumor cell expression of danger signals that stimulate innate immunity. The human abdominal cancer cell lines HT‑29, Panc‑01 and SK‑OV‑3 were exposed to different concentrations of hydrogen peroxide (H2O2), hypochlorous acid (HOCl) and peroxynitrite (ONOO). Metabolic activity was measured, as well as determination of cell death and danger signal expression levels via flow cytometry and detection of intracellular oxidation via high‑content microscopy. Oxidation of tumor decreased intracellular levels of the antioxidant glutathione and induced oxidation in mitochondria, accompanied by a decrease in metabolic activity and an increase in regulated cell death. At similar concentrations, HOCl showed the most potent effects. Non‑malignant HaCaT keratinocytes were less affected, suggesting the approach to be selective to some extent. Pro‑immunogenic danger molecules were investigated by assessing the expression levels of calreticulin (CRT), and heat‑shock protein (HSP)70 and HSP90. CRT expression was greatest following HOCl and ONOO treatment, whereas HOCl and H2O2 resulted in the greatest increase in HSP70 and HSP90 expression levels. These results suggested that HOCl may be a promising agent to complement current HIPEC regimens targeting peritoneal carcinomatosis.
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May-2021
Volume 45 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Freund E, Miebach L, Stope MB and Bekeschus S: Hypochlorous acid selectively promotes toxicity and the expression of danger signals in human abdominal cancer cells. Oncol Rep 45: 71, 2021
APA
Freund, E., Miebach, L., Stope, M.B., & Bekeschus, S. (2021). Hypochlorous acid selectively promotes toxicity and the expression of danger signals in human abdominal cancer cells. Oncology Reports, 45, 71. https://doi.org/10.3892/or.2021.8022
MLA
Freund, E., Miebach, L., Stope, M. B., Bekeschus, S."Hypochlorous acid selectively promotes toxicity and the expression of danger signals in human abdominal cancer cells". Oncology Reports 45.5 (2021): 71.
Chicago
Freund, E., Miebach, L., Stope, M. B., Bekeschus, S."Hypochlorous acid selectively promotes toxicity and the expression of danger signals in human abdominal cancer cells". Oncology Reports 45, no. 5 (2021): 71. https://doi.org/10.3892/or.2021.8022