Chemoprevention of pancreatic cancer: Characterization of par-4 and its modulation by 3,3′ diindolylmethane (DIM)

Asfar Sohail Azmi, Aamir Ahmad, Sanjeev Banerjee, Vivek M. Rangnekar, Ramzi M. Mohammad, Fazlul H. Sarkar

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

Purpose. Cancer chemoprevention is defined as the use of natural, synthetic, or biological agents to suppress, reverse or prevent the carcinogenic process from turning into aggressive cancer. Prostate apoptosis response-4 (Par-4) is a unique pro-apoptotic protein that selectively induces apoptosis in prostate cancer cells. However, its role in other malignancies has not been fully explored. This study tries to identify the functional significance of Par-4 in pancreatic cancer. Methods. Multiple molecular techniques such as Western blot analysis, trypan blue assay for cell viability, MTT assay for cell growth inhibition and Histone/DNA ELISA for apoptosis were used. Results. Western blot analysis revealed that 3,3′-diindolylmethane (DIM) a chemopreventive agent, specifically its more bioavailable formulation, B-DIM, at low doses (20 μmol/L) induces Par-4, in L3.6pl and Colo-357 pancreatic cancer cells. At similar doses, DIM reduced cell viability and caused cell growth inhibition and apoptosis. Moreover, DIM pre-treatment sensitized the cells to cytotoxic action of chemotherapeutic drug gemcitabine through up-regulation of Par-4. Conclusion. The induction of Par-4 is indirectly related to increased sensitivity and cell death through apoptosis. To our knowledge the results reported here showed, for the first time, the induction of Par-4 by chemopreventive agents, in general, and DIM, in particular, in pancreatic cancer cells in vitro.

Original languageEnglish
Pages (from-to)2117-2124
Number of pages8
JournalPharmaceutical Research
Volume25
Issue number9
DOIs
StatePublished - Sep 2008

Keywords

  • Apoptosis
  • B-DIM
  • Chemoprevention
  • Pancreatic cancer
  • Par-4

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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