Researchers Uncover Colorectal Cancer Cells' Dynamic Response to Hydrogen Peroxide

Researchers used HPICM and nanoelectrodes to study individual colorectal cancer cells' response to hydrogen peroxide gradients, revealing dynamic changes in cellular morphology and mechanical properties. The study found that eustress induced by low H2O2 levels increased cell stiffness, while high levels decreased it, and identified a novel interplay between cellular physical properties and biochemical signaling.

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Aqsa Younas Rana
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Researchers Uncover Colorectal Cancer Cells' Dynamic Response to Hydrogen Peroxide

Researchers Uncover Colorectal Cancer Cells' Dynamic Response to Hydrogen Peroxide

exploration, individual, cancer, cell A recent study published in the journal Science Bulletin has shed light on the dynamic response of individual living colorectal cancer cells to hydrogen peroxide (H2O2) gradients, specifically focusing on eustress, at the single-cell level and in real-time. Researchers from Kanazawa University's Nano Life Science Institute utilized hopping probe scanning ion conductance microscopy (HPICM) and highly sensitive platinum-functionalized nanoelectrodes to conduct the study.

Why this matters: This research has significant implications for the development of effective cancer treatments, as understanding how cancer cells respond to hydrogen peroxide can inform the design of targeted therapies. Furthermore, this study's findings could lead to the creation of innovative treatments for H2O2-related inflammatory diseases, which affect millions of people worldwide.

The study revealed that exposure to 0.1 or 1 mmol/L H2O2 eustress increased the extracellular to intracellular H2O2 gradient from 0.3 to 1.91 or 3.04, respectively. Additionally, the researchers found that F-actin-dependent cell stiffness increased under eustress of 0.1 mmol H2O2 but decreased under eustress of 1 mmol H2O2. Eustress-induced cell stiffness was positively regulated by AKT activation and negatively influenced the expression of the H2O2-scavenging enzyme GPX2, ultimately maintaining relatively stable cellular H2O2 levels.

exploring, effect, individual, cancer, cells, usin The implications of these findings are significant. The study suggests that the eustress induced by low levels of H2O2 may contribute to the failure of some H2O2-targeted therapies. The results uncover a novel interplay between cellular physical properties and biochemical signaling in cancer cells' antioxidant defense, shedding light on the utilization of H2O2 eustress for survival at the single-cell level. Inhibiting GPX under H2O2 eustress resulted in cytotoxicity, suggesting a potential enhancement for colon cancer treatment.

The study utilized HPICM to non-invasively investigate the cellular morphology and mechanical properties of individual colorectal cancer Caco-2 cells. Highly sensitive Pt-functionalized carbon nanoelectrodes enabled the measurement of dynamic changes in extracellular-to-intracellular H2O2 gradients of individual Caco-2 cells under H2O2 eustress conditions. The work was supported by the World Premier International Research Center Initiative (WPI), MEXT, Japan, and JSPS Grants-in-Aid for Scientific Research (21H01770, 22K04890).

The study, published on May 13, 2024, in Science Bulletin with the DOI 10.1016/j.scib.2024.04.004, was conducted by Dong Wang, Emily Woodcock, Xi Yang, Hiromi Nishikawa, Elena V Sviderskaya, Masanobu Oshima, Christopher Edwards, Yanjun Zhang, and Yuri Korchev. These groundbreaking findings provide crucial insights into the dynamic response of colorectal cancer cells to H2O2 gradients, paving the way for the development of innovative therapies targeting cancer and H2O2-related inflammatory diseases.

Key Takeaways

  • Researchers studied individual colorectal cancer cells' response to hydrogen peroxide (H2O2) gradients.
  • H2O2 eustress increased cell stiffness at low levels, but decreased it at high levels.
  • Cell stiffness was regulated by AKT activation and GPX2 expression.
  • Inhibiting GPX2 under H2O2 eustress led to cytotoxicity, suggesting a potential cancer treatment.
  • Findings could lead to innovative therapies for cancer and H2O2-related inflammatory diseases.