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Detection of Mitochondria Membrane Potential to Study CLIC4 Knockdown-induced HN4 Cell Apoptosis In Vitro

Published on: July 17, 2018

CLP induces apoptosis in human leukemia K562 cells through Ca(2+) regulating extracellular-related protein kinase ERK

C L Wang1, T B Ng, X H Cao

  • 1Department of Microbiology, College of Life Science, Nankai University, Tianjin, China.

Cancer Letters
|December 23, 2008
PubMed

Insights

Bacillus natto T-2 cyclic lipopeptide (CLP) triggers apoptosis in K562 leukemia cells by increasing intracellular calcium and activating ERK signaling. This pathway ultimately leads to programmed cell death.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Oncology

Background:

  • Cyclic lipopeptides (CLPs) are known to induce apoptosis in cancer cells.
  • The precise molecular mechanisms of CLP-induced apoptosis in human leukemic K562 cells remain unclear.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying CLP-induced apoptosis in K562 cells.
  • To investigate the role of intracellular calcium and specific signaling pathways in CLP's apoptotic effects.

Main Methods:

  • Purification of CLP from Bacillus natto T-2.
  • Measurement of intracellular calcium ([Ca2+]i) levels.
  • Assessment of apoptosis and Western blotting for ERK, p38, and JNK phosphorylation.
  • Inhibition studies using PD98059 (ERK inhibitor), SB203580 (p38 inhibitor), SP200125 (JNK inhibitor), and Bapta-AM (calcium chelator).

Main Results:

  • CLP treatment led to a sustained increase in intracellular calcium ([Ca2+]i).
  • CLP induced K562 cell apoptosis and ERK phosphorylation.
  • Apoptosis was reversed by an ERK inhibitor (PD98059) but not by p38 or JNK inhibitors.
  • Calcium chelation partially blocked CLP-induced apoptosis.
  • CLP-induced apoptosis involved the activation of Bax, cytochrome c, and caspase-3.

Conclusions:

  • CLP induces apoptosis in K562 cells via a mechanism involving increased intracellular calcium and subsequent ERK pathway activation.
  • The findings highlight the critical role of the calcium-ERK signaling axis in CLP-mediated apoptosis of human leukemia cells.

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