Abstract
Modified citrus pectin (MCP) is a carbohydrate enriched complex, which has been implicated in cancer treatment and prevention. However, the effects of MCP on urinary bladder cancer (UBC) are unknown. In this study, MCP was first tested in T24 and J82 human UBC cells and showed the inhibition of cell viability by the sulforhodamine B (SRB) assay. The MCP-treated UBC cells exhibited G2/M phase arrest with the decrease of Cyclin B1 and phosphorylated Cdc2. Caspase-3 was also activated, leading to the cleavage of Caspase-3 and PARP. We further explored the possible molecular mechanisms upon MCP treatment in UBC cells. Reduction of galectin-3 was observed and followed with the inactivation of Akt signaling pathway. Of note, galectin-3 knockdown by RNA interference recapitulated the MCP-mediated anti-proliferation, cell cycle arrest and apoptosis. Moreover, oral administration of MCP to the T24 xenograft-bearing nude mice inhibited the tumor growth significantly (P < 0.05). Quantification analysis of immunohistochemistry staining for Ki67 and cleaved Caspase-3 confirmed the decrease of proliferation index (P < 0.05) and the increase of apoptosis index (P < 0.01) in 700 mg/kg MCP-fed UBC xenografts. Using the information from TCGA database, we revealed that the overexpression of galectin-3 was associated with high tumor grade with lymph node metastasis, poor overall survival in UBC patients. Considering the remarkable inhibitory effects of MCP on UBC cell proliferation and survival in vitro and in vivo mainly through galectin-3, which is upregulated in UBCs, MCP may become an attractive agent, as a natural dietary fiber, for prevention and therapy of UBCs.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (81372168 to J. Y.), the Natural Science Foundation for Universities in Jiangsu Province (BK20151396 to J. Y.), One Hundred Talent Program of Chinese Academy of Sciences (to R. H.), and the Research Fund of Institutes for Drug Discovery and Development, Chinese Academy of Sciences (CASIMM0120164001 to R. H.). We thank the Institutional Technology Service Center of Shanghai Institute of Materia Medica for technical support.
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J. Y., and R. H. designed research; T. F., D. L., H. N., D. L., J. S., X. H., and Y. D. performed research and analyzed data; T. F., D. L., H. N., J. Y., and R. H. wrote the paper; and M. G., S. Y., J. Y., and R. H. provided supervision.
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Fang, T., Liu, Dd., Ning, Hm. et al. Modified citrus pectin inhibited bladder tumor growth through downregulation of galectin-3. Acta Pharmacol Sin 39, 1885–1893 (2018). https://doi.org/10.1038/s41401-018-0004-z
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DOI: https://doi.org/10.1038/s41401-018-0004-z
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