Abstract | BACKGROUND: Recent studies have demonstrated that side population (SP) cells isolated from various cancer cell lines and primary tumors possess stem cell-like properties. Sesamin, a food-derived agent, possesses anti- cancer activities both in vitro and in vivo. The present study was designed to determine whether sesamin also have effects on cancer stem-like SP cells from gallbladder cancer (GBC). METHODS: In this study, we sorted SP cells by flow cytometry. SP cells were cultured and treated with sesamin. Tumor-sphere formation, colony formation, Matrigel invasion and tumorigenic potential were determined. Expression of nuclear NF-κB, IL-6, p-Stat3, Twist, E-cadherin and Vimentin was measured by Western blot, immunofluorescence staining or RT-PCR analysis. Nuclear NF-κB activity and IL-6 protein level were assessed with ELISA. Xenograft tumors were generated in nude mice. RESULTS: After treated with sesamin, SP cells differentiated into cells expressing the epithelial marker ( E-cadherin). Sesamin effectively affected SP cells stem cell-like characteristics (i.e., tumor-sphere formation, colony-formation, Matrigel invasion), weakened the drug-resistance of SP cells and inhibited tumor growth both in vitro and in vivo. Treatment with sesamin significantly reduced the expression of nuclear NF-κB, IL-6, p-Stat3, Twist and Vimentin (a mesenchymal marker) in SP cells. Nuclear NF-κB activity and IL-6 level were also decreased after treatment with sesamin. CONCLUSION: Food-derived sesamin directs the epithelial differentiation of cancer stem-like SP cells from GBC, which is associated with attenuation of NF-κB-IL-6-Stat3-Twist signal pathway.
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Authors | Xiang Kong, Ming-zhe Ma, Yan Zhang, Ming-zhe Weng, Wei Gong, Li-qun Guo, Jun-xiu Zhang, Guo-dong Wang, Qing Su, Zhi-wei Quan, Jie-ren Yang |
Journal | BMC complementary and alternative medicine
(BMC Complement Altern Med)
Vol. 14
Pg. 254
(Jul 19 2014)
ISSN: 1472-6882 [Electronic] England |
PMID | 25038821
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cadherins
- Dioxoles
- Interleukin-6
- Lignans
- NF-kappa B
- sesamin
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Topics |
- Analysis of Variance
- Animals
- Cadherins
(metabolism)
- Carcinoma
(drug therapy, metabolism, pathology)
- Cell Differentiation
(drug effects)
- Cell Line, Tumor
- Dioxoles
(pharmacology)
- Female
- Gallbladder Neoplasms
(drug therapy, metabolism, pathology)
- Humans
- Interleukin-6
(metabolism)
- Lignans
(pharmacology)
- Mice
- Mice, Nude
- NF-kappa B
(metabolism)
- Neoplastic Stem Cells
(drug effects, metabolism, pathology)
- Side-Population Cells
(drug effects, metabolism, pathology)
- Signal Transduction
(drug effects)
- Xenograft Model Antitumor Assays
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