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The novel AKT inhibitor afuresertib suppresses human Merkel cell carcinoma MKL-1 cell growth

J H Wu1,2, A L Limmer1, D Narayanan1

  • 1Department of Dermatology, McGovern Medical School at The University of Texas Health Science Center, Houston, TX, USA.

Clinical and Experimental Dermatology
|June 11, 2021
PubMed

Insights

Afuresertib, an AKT inhibitor, effectively reduces Merkel cell carcinoma (MCC) cell proliferation. This study highlights AKT signaling

Area of Science:

  • Oncology
  • Molecular Biology
  • Dermatology

Background:

  • Merkel cell carcinoma (MCC) is an aggressive skin cancer with a poor prognosis.
  • The AKT/mammalian target of rapamycin (mTOR) pathway is crucial for Merkel cell carcinogenesis, regulating cell survival and protein synthesis.

Purpose of the Study:

  • To investigate the regulatory role of AKT in MCC cells.
  • To evaluate the effects of the novel AKT inhibitor, afuresertib, on MCC proliferation and signaling pathways.

Main Methods:

  • Treatment of MCC cells with afuresertib, a novel ATP-competitive AKT inhibitor.
  • Analysis of downstream signaling pathways, including mTOR, glycogen synthase kinase 3, and apoptotic markers.
  • Assessment of p16 expression and B-cell lymphoma-2-associated death promoter phosphomodulation.

Main Results:

  • Afuresertib treatment deactivated mTOR and glycogen synthase kinase 3 pathway proteins in MCC cells.
  • Inhibition of AKT by afuresertib led to increased activation of proapoptotic pathways.
  • Afuresertib significantly inhibited MCC cell proliferation through upregulation of p16 and modulation of proapoptotic factors.

Conclusions:

  • AKT plays a significant regulatory role in MCC cell proliferation.
  • Afuresertib demonstrates potent anti-proliferative effects on MCC cells.
  • AKT inhibition, using agents like afuresertib, shows potential for future clinical management of Merkel cell carcinoma.

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