Abstract | PURPOSE: 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 micromol/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.
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Authors | Asfar Sohail Azmi, Aamir Ahmad, Sanjeev Banerjee, Vivek M Rangnekar, Ramzi M Mohammad, Fazlul H Sarkar |
Journal | Pharmaceutical research
(Pharm Res)
Vol. 25
Issue 9
Pg. 2117-24
(Sep 2008)
ISSN: 0724-8741 [Print] United States |
PMID | 18427961
(Publication Type: Journal Article)
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Chemical References |
- Anticarcinogenic Agents
- Antineoplastic Agents
- Indoles
- Receptors, Thrombin
- Deoxycytidine
- protease-activated receptor 4
- Cisplatin
- 3,3'-diindolylmethane
- Gemcitabine
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Topics |
- Anticarcinogenic Agents
(pharmacology)
- Antineoplastic Agents
(pharmacology)
- Apoptosis
(drug effects)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Cell Survival
(drug effects)
- Cisplatin
(pharmacology)
- Deoxycytidine
(analogs & derivatives, pharmacology)
- Drug Synergism
- Humans
- Indoles
(pharmacology)
- Pancreatic Neoplasms
(metabolism, pathology, prevention & control)
- Receptors, Thrombin
(metabolism)
- Signal Transduction
(drug effects)
- Up-Regulation
- Gemcitabine
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