Differentiation therapy: sesamin as an effective agent in targeting cancer stem-like side population cells of human gallbladder carcinoma.

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.

• 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)

Chemical References

• Cadherins
• Dioxoles
• Interleukin-6
• Lignans
• NF-kappa B
• sesamin

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