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Modified citrus pectin inhibited bladder tumor growth through downregulation of galectin-3

Tian Fang1, Dan-Dan Liu2,3, He-Ming Ning2,3,4

  • 1Department of Comparative Medicine, Jinling Hospital, Clinical School of Medical College of Nanjing University, Nanjing, 210002, China.

Acta Pharmacologica Sinica
|May 18, 2018
PubMed

Insights

Modified citrus pectin (MCP) shows promise in treating and preventing urinary bladder cancer (UBC). This natural dietary fiber inhibits UBC cell growth and survival by targeting galectin-3, offering a potential therapeutic agent.

Area of Science:

  • Oncology
  • Nutritional Science
  • Molecular Biology

Background:

  • Modified citrus pectin (MCP) is recognized for its potential in cancer treatment and prevention.
  • The specific effects of MCP on urinary bladder cancer (UBC) remain largely unexplored.

Purpose of the Study:

  • To investigate the efficacy of MCP in inhibiting human UBC cell lines and xenograft tumor growth.
  • To elucidate the underlying molecular mechanisms of MCP's anti-cancer effects in UBC, focusing on galectin-3 and associated signaling pathways.

Main Methods:

  • In vitro studies utilized T24 and J82 human UBC cells to assess cell viability, cell cycle progression, apoptosis, and molecular targets (galectin-3, Akt pathway).
  • In vivo efficacy was evaluated in T24 xenograft-bearing nude mice treated with MCP, with tumor growth and cellular markers (Ki67, cleaved Caspase-3) analyzed.
  • TCGA database analysis correlated galectin-3 expression with UBC patient outcomes.

Main Results:

  • MCP significantly inhibited UBC cell viability, induced G2/M phase arrest, and promoted apoptosis by activating Caspase-3 and cleaving PARP.
  • MCP treatment led to reduced galectin-3 expression and inactivation of the Akt signaling pathway.
  • Galectin-3 knockdown mimicked MCP's anti-proliferative and pro-apoptotic effects.
  • In vivo, MCP administration suppressed tumor growth, decreased proliferation (Ki67), and increased apoptosis (cleaved Caspase-3) in UBC xenografts.
  • Overexpression of galectin-3 in UBC patients correlated with advanced tumor grade, lymph node metastasis, and poorer survival.

Conclusions:

  • Modified citrus pectin demonstrates significant anti-cancer properties against urinary bladder cancer in vitro and in vivo.
  • The anti-tumor effects of MCP are mediated, at least in part, through the downregulation of galectin-3 and subsequent modulation of the Akt pathway.
  • Given its efficacy and the crucial role of galectin-3 in UBC progression, MCP presents a promising natural agent for UBC prevention and therapy.
Keywords:
cell survivalgalectin-3modified citrus pectinurinary bladder cancerxenograft

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