2. Academic Validation
  3. 25-hydroxycholesterol-induced cell death via activation of ROCK/LIMK/cofilin axis in colorectal cancer cell spheroids

25-hydroxycholesterol-induced cell death via activation of ROCK/LIMK/cofilin axis in colorectal cancer cell spheroids

  • J Steroid Biochem Mol Biol. 2022 Feb;216:106037. doi: 10.1016/j.jsbmb.2021.106037.
Ayaho Hitsuda 1,  Reona Dan 1,  Ayaka Urakawa 1,  Yasuna Hiraoka 1,  Chiho Murakami 1,  Hideya Yamamoto 1,  Arowu R Tanaka 2
Affiliations

Affiliations

  • 1 Faculty of Pharmacy, Yasuda Women's University, 6-13-1 Yasuhigashi, Asaminami Ward, Hiroshima City, Hiroshima 731-0153, Japan.
  • 2 Faculty of Pharmacy, Yasuda Women's University, 6-13-1 Yasuhigashi, Asaminami Ward, Hiroshima City, Hiroshima 731-0153, Japan. Electronic address: [email protected].
PMID: 34861388 DOI: 10.1016/j.jsbmb.2021.106037
Abstract

25-Hydroxycholesterol (25OHC) induces anchorage-dependent programmed cell death, or anoikis, in colorectal Cancer cells but the mechanism is not fully understood. Here, we found that 25OHC induced cofilin phosphorylation and promoted rearrangement of the actin Cytoskeleton in spheroids of the colorectal Cancer cell lines, DLD1 and HT29/WiDr. Cell death induced by 25OHC was inhibited by the actin polymerization inhibitor, cytochalasin D, and BMS-3, an inhibitor of LIMK, which phosphorylates and inactivates cofilin. In addition, we showed that cofilin phosphorylation induced by 25OHC was associated with Caspase-3 activation, which can activate ROCK. Rho GTPase was directly activated by 25OHC. These results indicate that 25OHC affects actin dynamics through activation of the Rho/ROCK/LIMK/cofilin axis, eventuating in the cell death of colorectal Cancer cell spheroids.

Keywords

25-hydroxycholesterol; Anoikis; Caspase-3; Cofilin; LIMK; Rho; Spheroid.

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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-12466
    ≥98.0%, Caspase-3 Inhibitor