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Single-agent Adavosertib Shows Anticancer Effects Against Colorectal Cancer Cells

Mai Ly Thi Nguyen1, Chi Pham2, Tai Suc Nguyen2,3

  • 1Department of Biochemistry, Military Hospital 103, Hanoi, Vietnam.

Anticancer Research
|October 30, 2024
PubMed
Abstract

Insights

Adavosertib monotherapy effectively inhibits colorectal cancer cells by halting cell cycle progression. This WEE1 kinase inhibitor shows promise as a targeted therapy for colorectal cancer, even in TP53-wildtype cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Cycle Regulation

Background:

  • Colorectal cancer (CRC) is a leading cause of cancer death worldwide.
  • Adavosertib (AZD1775) is a WEE1 kinase inhibitor that causes DNA damage and cell death.
  • Previous studies show adavosertib's efficacy in combination therapy for p53-mutated cancers.

Purpose of the Study:

  • To evaluate adavosertib as a monotherapy in TP53-wildtype human colorectal cancer cells (HCT116).
  • To investigate the mechanism of WEE1 kinase inhibition by adavosertib in this context.

Main Methods:

  • HCT116 cells were treated with varying concentrations of adavosertib (24-72 hours).
  • Cell viability was measured using WST-1 and crystal violet assays.
  • Cell migration, cell cycle distribution, and apoptosis were analyzed via wound healing and flow cytometry.

Main Results:

  • Adavosertib demonstrated an IC50 of 0.1310 μM in HCT116 cells.
  • Monotherapy significantly reduced cell viability and inhibited cell migration.
  • Adavosertib abrogated intra-S phase cell cycle arrest and induced apoptosis at 0.250 μM.

Conclusions:

  • Adavosertib monotherapy effectively inhibits TP53-wildtype HCT116 colorectal cancer cells.
  • The drug functions by abrogating intra-S phase cell cycle arrest.
  • Adavosertib presents a potential targeted therapy strategy for colorectal cancer.
Keywords:
AdavosertibHCT116 cancer cellsWEE1 kinasecolorectal cancermonotherapy

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