Abstract | BACKGROUND: METHODS: RESULTS:
Diindolylmethane treatment induced apoptosis in all six ovarian cancer cell lines. Phosphorylation of STAT3 at Tyr-705 and Ser-727 was reduced by DIM in a concentration-dependent manner. In addition, diindolylmethane treatment inhibited nuclear translocation, DNA binding, and transcriptional activity of STAT3. Interleukin (IL)-6-induced phosphorylation of STAT3 at Tyr-705 was significantly blocked by DIM. Overexpression of STAT3 by gene transfection blocked DIM-induced apoptosis. In addition, DIM treatment reduced the levels of IL-6 in ovarian cancer cells and in the tumors. DIM treatment also inhibited cell invasion and angiogenesis by suppressing hypoxia-inducible factor 1α (HIF-1α) and vascular epithelial growth factor ( VEGF). Importantly, diindolylmethane treatment potentiated the effects of cisplatin in SKOV-3 cells by targeting STAT3. Oral administration of 3 mg diindolylmethane per day and subsequent administration of cisplatin substantially inhibited in vivo tumor growth. Western blotting analysis of tumor lysates indicated increased apoptosis and reduced STAT3 activation. CONCLUSIONS:
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Authors | Prabodh K Kandala, Sanjay K Srivastava |
Journal | BMC medicine
(BMC Med)
Vol. 10
Pg. 9
(Jan 26 2012)
ISSN: 1741-7015 [Electronic] England |
PMID | 22280969
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- HIF1A protein, human
- Hypoxia-Inducible Factor 1, alpha Subunit
- Indoles
- Interleukin-6
- STAT3 Transcription Factor
- Vascular Endothelial Growth Factor A
- Cisplatin
- 3,3'-diindolylmethane
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Topics |
- Animals
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Apoptosis
(drug effects)
- Cell Growth Processes
(drug effects)
- Cell Line, Tumor
- Cisplatin
(administration & dosage, adverse effects)
- Disease Models, Animal
- Drug Synergism
- Female
- Humans
- Hypoxia-Inducible Factor 1, alpha Subunit
(genetics, metabolism)
- Indoles
(administration & dosage, adverse effects)
- Interleukin-6
(genetics, metabolism)
- Mice
- Ovarian Neoplasms
(drug therapy, pathology)
- Phosphorylation
(drug effects)
- STAT3 Transcription Factor
(metabolism)
- Transcriptional Activation
(drug effects)
- Vascular Endothelial Growth Factor A
(genetics, metabolism)
- Xenograft Model Antitumor Assays
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