Alisertib induces apoptosis and autophagy through targeting the AKT/mTOR/AMPK/p38 pathway in leukemic cells

Yunfeng Fu1, Yanan Zhang1, Meng Gao1

  • 1The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China.

Insights

Alisertib, an Aurora kinase A inhibitor, effectively inhibits leukemia cell growth, inducing apoptosis and autophagy. This study reveals its mechanism involves suppressing key signaling pathways, highlighting alisertib as a potential leukemia treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Alisertib is a potent Aurora kinase A inhibitor with demonstrated anti-cancer effects.
  • The precise molecular mechanisms underlying alisertib's effects on leukemia, particularly apoptosis and autophagy, remain unclear.

Purpose of the Study:

  • To investigate the impact of alisertib on leukemia cell growth, apoptosis, and autophagy.
  • To elucidate the molecular pathways involved in alisertib-induced cell death and autophagy in leukemia cells.

Main Methods:

  • Utilized acid phosphatase, MTT, and Annexin V/propidium iodide assays for cell viability and apoptosis.
  • Employed immunostaining for light chain 3B and Western blot analysis to assess autophagy and signaling pathway activity.

Main Results:

  • Alisertib significantly inhibited REH leukemia cell line growth in a dose-dependent manner.
  • Alisertib treatment induced both apoptosis and autophagy in leukemia cells.
  • Western blot analysis indicated suppression of Akt/mTOR/AMPK/p38 MAPK signaling pathways.

Conclusions:

  • Alisertib exhibits potent anti-leukemic effects by inducing apoptosis and autophagy.
  • The mechanism involves the suppression of critical signaling pathways, including Akt/mTOR/AMPK/p38 MAPK.
  • Alisertib shows promise as an autophagy-inducing therapeutic agent for leukemia treatment.

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