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Doxycycline induces caspase-dependent apoptosis in human pancreatic cancer cells

Petros X E Mouratidis1, Kay W Colston, Angus G Dalgleish

  • 1Division of Oncology, Department of Cellular and Molecular Medicine, St. George's University of London, London, United Kingdom.

International Journal of Cancer
|November 30, 2006
PubMed

Insights

Doxycycline (DC) exhibits pro-apoptotic effects in pancreatic cancer cells, reducing proliferation. This mechanism involves caspase activation and the p38MAPK pathway, offering potential new treatment strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Pancreatic cancer remains a significant challenge with limited effective chemotherapy options.
  • Doxycycline (DC), a tetracycline antibiotic, is explored for novel therapeutic applications.
  • Understanding the molecular mechanisms of pancreatic cancer is crucial for developing new treatments.

Purpose of the Study:

  • To investigate the pro-apoptotic effects of Doxycycline (DC) in pancreatic adenocarcinoma cell lines.
  • To elucidate the molecular pathways mediating DC-induced apoptosis in pancreatic cancer.
  • To assess the impact of DC on cell proliferation and apoptosis signaling.

Main Methods:

  • Cell proliferation was quantified using the Sulforhodamine B (SRB) assay.
  • Apoptosis induction was measured via Enzyme-Linked Immunosorbent Assay (ELISA).
  • Caspase activation, protein expression, and post-translational modifications were analyzed using immunoblotting and colorimetric assays.

Main Results:

  • Doxycycline (DC) treatment significantly reduced proliferation in T3M4 and GER pancreatic cancer cell lines.
  • DC induced caspase-dependent apoptosis, activating caspases 3, 7, 8, 9, 10, and increasing FADD levels.
  • Inhibition of caspase-8 or caspase-10, but not caspase-9, attenuated DC-induced apoptosis.
  • DC increased Bax protein levels and phosphorylated p38MAPK pathway components (p38MAPK, MKK3/6, MAPKAPK2).

Conclusions:

  • Doxycycline (DC) demonstrates pro-apoptotic effects in pancreatic cancer cells.
  • The mechanism involves caspase-dependent apoptosis, particularly via caspase-8 and caspase-10 activation.
  • DC influences the p38MAPK pathway, contributing to its anti-cancer activity.

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