The effect of paclitaxel on apoptosis, autophagy and mitotic catastrophe in AGS cells

Tin Myo Khing1, Won Seok Choi1, Dong Min Kim1

  • 1Laboratory of Signaling and Pharmacological Activity, Department of Pharmacology, College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea.

Scientific Reports
|December 7, 2021
PubMed

Insights

Paclitaxel triggers gastric cancer cell death through mitotic catastrophe, autophagy, and apoptosis. This study clarifies the complex mechanisms of paclitaxel

Area of Science:

  • Oncology
  • Cell Biology
  • Pharmacology

Background:

  • Paclitaxel is an anti-microtubule chemotherapy agent.
  • Its precise mechanism of cell death induction in gastric cancer remains incompletely understood.

Purpose of the Study:

  • To elucidate the detailed mechanisms by which paclitaxel induces cell death in AGS gastric cancer cells.
  • To investigate the roles of apoptosis, autophagy, and mitotic catastrophe in paclitaxel's action.

Main Methods:

  • Treatment of AGS cells with paclitaxel.
  • Analysis of apoptosis markers (caspase-3, caspase-9, PARP).
  • Assessment of autophagy markers (LC3B-II, Atg5, PI3K, Beclin-1, p62).
  • Evaluation of cell cycle progression, mitotic catastrophe, and senescence markers (CDC2, CDC25C, lamin B1).

Main Results:

  • Paclitaxel induced intrinsic apoptosis via caspase and PARP activation.
  • Autophagy was confirmed by increased LC3B-II and associated proteins, and decreased p62.
  • Paclitaxel caused G2/M cell cycle arrest, multinucleation, and mitotic catastrophe within 24 hours.
  • Cells subsequently underwent senescence, indicated by decreased CDC2, CDC25C, and lamin B1 expression after 48 hours.

Conclusions:

  • Paclitaxel-induced cell death in AGS cells involves a coordinated interplay of apoptosis, autophagy, and mitotic catastrophe.
  • Mitotic catastrophe is a crucial component of paclitaxel's anti-cancer effect in gastric cancer cells.

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