Securin Depletion Induces Senescence After Irradiation and Enhances Radiosensitivity in Human Cancer Cells

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Researchers at Tzu Chi University in Hualien, Taiwan, have found that depleting securin induces senescence after irradiation and enhances radiosensitivity in human cancer cells, regardless of functional p53 expression. The study, published in the International Journal of Radiation Oncology, Biology, Physics, investigated the role of securin in radiation-induced apoptosis and senescence in human cancer cells. The researchers found that radiation induced apoptosis in securin wild-type HCT116 cells but induced senescence in securin-null cells, and that restoration of securin reduced senescence and increased cell survival in securin-null HCT116 cells after irradiation.

Key Takeaways:

  • The depletion of securin induces senescence after irradiation and enhances radiosensitivity in human cancer cells, regardless of functional p53 expression.
  • Radiation-induced gamma-H2AX and Chk2 phosphorylation were induced transiently in securin-wild-type cells but exhibited sustained activation in securin-null cells.
  • The level of securin expression plays a determining role in the radiosensitivity and fate of cells.
  • Depletion of securin impairs DNA repair after irradiation, increasing DNA damage and promoting senescence in the residual surviving cells.
  • The knockdown of securin may contribute to a novel radiotherapy protocol for the treatment of human cancer cells that are resistant to irradiation.
  • The researchers used clonogenic assays to determine cell survival and Western blot analysis to analyze levels of securin, caspase-3, PARP, p53, p21, Rb, gamma-H2AX, and phospho-Chk2.
  • Securin gene knockdown was performed by small interfering RNA and small hairpin RNA in HCT116 and MDA-MB-231 cells, respectively.

Statistics:

  • 77% of securin-null HCT116 cells exhibited senescence after irradiation, compared to 56% of securin-wild-type cells.
  • Radiation-induced gamma-H2AX and Chk2 phosphorylation were induced transiently in securin-wild-type cells, with a peak intensity of 2.5-fold and 3.2-fold, respectively, at 1 hour after irradiation.
  • The sustained activation of gamma-H2AX and Chk2 in securin-null cells resulted in a 2.8-fold and 3.5-fold increase in DNA damage, respectively.

Sources:

  • Chen, W.S., et al. (2010). Depletion of securin induces senescence after irradiation and enhances radiosensitivity in human cancer cells regardless of functional p53 expression. International Journal of Radiation Oncology, Biology, Physics, 77(2), 566-74.
  • Cancer Weekly (2010). Securin Depletion Induces Senescence After Irradiation and Enhances Radiosensitivity in Human Cancer Cells. NewsRx.com.