Fucoidan Induces Apoptosis of HT-29 Cells via the Activation of DR4 and Mitochondrial Pathway

Area of Science:

• Marine biotechnology
• Cancer research
• Molecular biology

Background:

• Fucoidan exhibits diverse pharmacological effects.
• The precise mechanism of fucoidan-induced apoptosis in colorectal cancer (CRC) cells requires further elucidation.

Purpose of the Study:

• To investigate the molecular mechanisms underlying fucoidan-induced apoptosis in HT-29 CRC cells.
• To identify the specific signaling pathways and molecular targets involved in fucoidan's anti-cancer effects.

Main Methods:

• Utilized HT-29 colorectal cancer cells.
• Employed siRNA to silence DR4 expression.
• Assessed cell viability, mitochondrial membrane potential, and cytochrome C release.
• Investigated DR4 activation at transcriptional and protein levels.

Main Results:

• Fucoidan induced apoptosis in HT-29 cells via JNK signaling pathway activation.
• Fucoidan upregulated DR4 expression, contributing to apoptosis.
• Silencing DR4 significantly increased cell survival.
• Fucoidan disrupted mitochondrial membrane potential and integrity.
• Both DR4 (extrinsic) and mitochondrial (intrinsic) pathways are involved, with the extrinsic pathway acting upstream.

Conclusions:

• Fucoidan induces colorectal cancer cell apoptosis through a mechanism involving DR4 activation and mitochondrial dysfunction.
• The extrinsic pathway initiated by DR4 activation precedes the intrinsic mitochondrial pathway.
• This study provides a mechanistic basis for fucoidan's potential as a CRC therapeutic agent.