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Curcumin increases exosomal TCF21 thus suppressing exosome-induced lung cancer.

ABSTRACT: Curcumin is a novel drug for lung cancer treatment. However, the mechanism underlying the anti-tumor effect of curcumin remains elusive. Previous evidences indicated that, the methylating transferase DNMT1 is downregulated by curcumin, and the transcription factor 21 (TCF21) is suppressed by DNMT1. We hereby attempt to elucidate the correlation between curcumin treatment and TCF21 expression. Exosomes derived from curcumin-pretreated H1299 cells were used to treat BEAS-2B cells, which induced proliferation, colony formation and migration of BEAS-2B cells. An increase in TCF21 expression in response to curcumin was also seen, as revealed by real-time PCR (RT-PCR) and western blot. Analysis using the GEO database (access #GSE21210) indicated that a positive correlation existed between TCF21 levels and lung cancer patient survival. TCF21 overexpression and knockdown was introduced to H1299 cells through lentiviral system, which led to suppression and promotion of tumor growth, respectively. We also demonstrated that DNMT1 expression was downregulated by curcumin. Therefore, curcumin exerts its anti-cancer function by downregulating DNMT1, thereby upregulating TCF21.

SUBMITTER: Wu H

PROVIDER: S-EPMC5349972 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Curcumin increases exosomal TCF21 thus suppressing exosome-induced lung cancer.

Wu Hao H Zhou Jingcheng J Zeng Chao C Wu Da D Mu Zhimin Z Chen Baokun B Xie Yuancai Y Ye Yiwang Y Liu Jixian J

Oncotarget 20161201 52

Curcumin is a novel drug for lung cancer treatment. However, the mechanism underlying the anti-tumor effect of curcumin remains elusive. Previous evidences indicated that, the methylating transferase DNMT1 is downregulated by curcumin, and the transcription factor 21 (TCF21) is suppressed by DNMT1. We hereby attempt to elucidate the correlation between curcumin treatment and TCF21 expression. Exosomes derived from curcumin-pretreated H1299 cells were used to treat BEAS-2B cells, which induced pr ...[more]

PMID: 27894084

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Project description:The precise mechanism of intercellular communication among cancer cells after radiation exposure remains unclear. Exosomes are membrane-enclosed small vesicles constituted by lipid bilayers and are recognized as mediators of intercellular communication that transport a variety of intracellular components, including microRNA (miRNA). Here we identified novel roles of exosomes released from irradiated cells to neighboring cancer cells. To confirm the presence of exosomes in the culture media of the human pancreatic cancer cell line MIAPaCa-2, ultracentrifugation was performed followed by transmission electron microscopy and nanoparticle tracking analysis (NanoSight) using the exosome-specific surface markers CD9 and CD63. Subsequent endocytosis of exosomes was confirmed by fluorescent microscopy. Cell survival after irradiation and following the addition of exosomes was evaluated by a colony-forming assay. Expression of miRNAs in exosomes was then quantified by microarray analysis, while those of Cu/Zn superoxide dismutase (SOD1) and Mn-superoxide dismutase (SOD2) enzymes in MIAPaCa-2 cells were evaluated by western blotting. Results showed that the uptake of irradiated exosomes was significantly higher than that of non-irradiated exosomes. Notably, irradiated exosomes induced higher intracellular levels of ROS and a higher frequency of DNA damage in MIAPaCa-2 cells, as determined by fluorescent microscopy and immunocytochemistry, respectively. Moreover, six upregulated and five downregulated miRNAs were identified in 5 Gy- and 8 Gy-irradiated cells using miRNA microarray analyses. Further analyses using miRNA-mimics and real time reverse transcription PCR identified miR-6823-5p as a possible candidate for SOD1 inhibition, leading to increased intracellular ROS level and DNA damage. This is the first study to demonstrate that irradiated exosomes can enhance the radiation effect via increased intracellular ROS levels in cancer cells, potentially leading to improved understanding of the bystander effect of neighboring cancer cells.

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Curcumin increases exosomal TCF21 thus suppressing exosome-induced lung cancer.

Publications

Curcumin increases exosomal TCF21 thus suppressing exosome-induced lung cancer.

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