Journal
INTERNATIONAL JOURNAL OF ONCOLOGY
Volume 47, Issue 6, Pages 2064-2072Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2015.3202
Keywords
curcumin; cancer-associated fibroblasts; monoamine oxidase A/mammalian target of rapamycin/hypoxia-inducible factor-1 alpha signaling; prostate cancer; invasion
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Funding
- National Science Foundation of China [81372736, 81072107]
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Cancer-associated fibroblasts (CAFs) are key determinants in the malignant progression of cancer, supporting tumorigenesis and metastasis. CAFs also mediate epithelial to mesenchymal transition (EMT) in tumor cells and their achievement of stem cell traits. Curcumin has recently been found to possess anticancer activities via its effect on a variety of biological pathways involved in cancer progression. In this study, we found that CAFs could induce prostate cancer cell EMT and invasion through a monoamine oxidase A (MAOA)/ mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1 alpha (HIF-1 alpha) signaling pathway, which exploits reactive oxygen species (ROS) to drive a migratory and aggressive phenotype of prostate carcinoma cells. Moreover, CAFs was able to increase CXC chemokine receptor 4 (CXCR4) and interleukin-6 (IL-6) receptor expression in prostate cancer cells. However, curcumin abrogated CAF-induced invasion and EMT, and inhibited ROS production and CXCR4 and IL-6 receptor expression in prostate cancer cells through inhibiting MAOA/mTOR/HIF-1 alpha signaling, thereby supporting the therapeutic effect of curcumin in prostate cancer.
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