Curcumin inhibits cancer-associated fibroblast-driven prostate cancer invasion through MAOA/mTOR/HIF-1α signaling.
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-1α (HIF-1α) 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-1α signaling, thereby supporting the therapeutic effect of curcumin in prostate cancer.
Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
Yuefeng
Y
Du
Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
Qingzhi
Q
Long
Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
Lin
L
Zhang
Department of Urology, Tongji Medical College Union Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
Ying
Y
Shi
School of Life Science and Technology, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
Xioagang
X
Liu
Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
Xudong
X
Li
Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
Bin
B
Guan
Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
Yanchao
Y
Tian
Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
Xinyang
X
Wang
Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
Lei
L
Li
Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
Dalin
D
He
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D008995:Monoamine Oxidase / Q000378:metabolism; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
D000970:Antineoplastic Agents; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008995:Monoamine Oxidase; C579458:monoamine oxidase A, human; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D003474:Curcumin