title: Low-concentration capsaicin promotes colorectal cancer metastasis by triggering ROS production and modulating Akt/mTOR and STAT-3 pathways.
abstract: Colorectal cancer (CRC), one of the most common human malignancies, is a major public health problem in the developed world. Capsaicin, widely used as a food additive and as an analgesic agent, is a major pungent ingredient of red pepper. Though capsaicin-induced apoptosis was previously reported in cancer cells, relatively little is known about the impact of capsaicin on other aspect of cancer cell behavior. In this study, we demonstrated that treatment with high-concentration of capsaicin (≥ 200 µM for SW480 and CT-26 cell lines; ≥ 25 µM for HCT116 cell line) inhibited CRC cell proliferation in a dose-dependent manner. In spite of no anti-proliferative effect, notably, low-concentration of capsaicin (100 µM for SW480 and CT-26 cell lines; 12.5 µM for HCT116 cell line) enhanced both migratory and invasive capability of these cells, which was validated by both in vitro and in vivo model. Further, we showed that 100 µM capsaicin induced epithelial-to-mesenchymal (EMT), up-regulated expression of MMP-2 and MMP-9, and activated Akt/mTOR and STAT-3 pathways in SW480 cells. Finally, we showed that capsaicin-induced metastasis of CRC cells was mediated by modulating reactive oxygen species (ROS) production. Our findings are considered a significant step toward a better understanding of capsaicin-associated regulatory network on CRC cells.
authors.affiliation: Chengdu Medical College, Chengdu, People' Republic of China.
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.forename: T Z
authors.initials: TZ
authors.lastname: Li
authors.forename: G H
authors.initials: GH
authors.lastname: Xu
authors.forename: B B
authors.initials: BB
authors.lastname: Luo
authors.forename: Y X
authors.initials: YX
authors.lastname: Chen
authors.forename: T
authors.initials: T
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000502:physiology*
chemical_list: D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D002211:Capsaicin