Antimetastatic effects of gossypol on colon cancer cells by targeting the u-PA and FAK pathways.

Abstract

Metastasis is the most prevalent cause of treatment failure in patients with colon cancer. Gossypol is reported to exhibit antioxidant, anticancer, antivirus and antimicrobial properties. However, the effects of gossypol on cancer invasion and tumour growth of human colon cancer remain unclear. This study aimed to provide molecular evidence associated with the antimetastatic and anti-tumour effects of gossypol on human colorectal carcinoma (CRC) cells. Gossypol inhibited the viability of human colon cancer cells in a dose-dependent manner. Gossypol was sufficient to reduce the invasion, migration and adhesion in DLD-1 and COLO 205 cells. Zymography and western blot assay showed that gossypol reduced the activities and protein expression of urokinase-type plasminogen activator (u-PA), respectively. Gossypol suppressed the level of p-focal adhesion kinase (FAK) and epithelial-to-mesenchymal transition markers, including N-cadherin, fibronectin and vimentin. Gossypol also inhibited the lung metastasis of DLD-1 cells, as indicated by the nude mouse model. These results suggested that gossypol inhibited the metastatic properties of human colon cancer cells by targeting u-PA through the FAK pathway, suggesting that gossypol could be used as an adjuvant therapeutic agent for the treatment of human colon cancer cells.

• Authors: She-Fang Huang , Shu-Chen Chu , Li-Sung Hsu , Yu-Chen Tu , Pei-Ni Chen , Yih-Shou Hsieh
• Journal: Food & function (Food Funct) Vol. 10 Issue 12 Pg. 8172-8181 (Dec 11 2019) ISSN: 2042-650X [Electronic] England
• PMID: 31730141 (Publication Type: Journal Article)

Chemical References

• Cadherins
• Fibronectins
• Vimentin
• Focal Adhesion Protein-Tyrosine Kinases
• Urokinase-Type Plasminogen Activator
• Gossypol

Topics

• Animals
• Cadherins (genetics, metabolism)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Survival (drug effects)
• Colonic Neoplasms (drug therapy, genetics, metabolism, pathology)
• Epithelial-Mesenchymal Transition (drug effects)
• Fibronectins (genetics, metabolism)
• Focal Adhesion Protein-Tyrosine Kinases (genetics, metabolism)
• Gossypol (administration & dosage)
• Humans
• Lung Neoplasms (prevention & control, secondary)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Metastasis (prevention & control)
• Urokinase-Type Plasminogen Activator (genetics, metabolism)
• Vimentin (genetics, metabolism)