Selective Inhibition of Liver Cancer Cells Using Venom Peptide.

Abstract

Increasingly cancer is being viewed as a channelopathy because the passage of ions via ion channels and transporters mediate the regulation of tumor cell survival, death, and motility. As a result, a potential targeted therapy for cancer is to use venom peptides that are selective for ion channels and transporters overexpressed in tumor cells. Here we describe the selectivity and mechanism of action of terebrid snail venom peptide, Tv1, for treating the most common type of liver cancer, hepatocellular carcinoma (HCC). Tv1 inhibited the proliferation of murine HCC cells and significantly reduced tumor size in Tv1-treated syngeneic tumor-bearing mice. Tv1's mechanism of action involves binding to overexpressed transient receptor potential (TRP) channels leading to calcium dependent apoptosis resulting from down-regulation of cyclooxygenase-2 (COX-2). Our findings demonstrate the importance of modulating ion channels and the unique potential of venom peptides as tumor specific ligands in the quest for targeted cancer therapies.

• Authors: Prachi Anand, Petr Filipenko, Jeannette Huaman, Michael Lyudmer, Marouf Hossain, Carolina Santamaria, Kelly Huang, Olorunseun O Ogunwobi, Mandë Holford
• Journal: Marine drugs (Mar Drugs) Vol. 17 Issue 10 (Oct 17 2019) ISSN: 1660-3397 [Electronic] Switzerland
• PMID: 31627357 (Publication Type: Journal Article)

Chemical References

• Mollusk Venoms
• Peptides
• Cyclooxygenase 2

Topics

• Animals
• Apoptosis (drug effects)
• Carcinoma, Hepatocellular (drug therapy, metabolism)
• Cell Line
• Cell Line, Tumor
• Cyclooxygenase 2 (metabolism)
• Down-Regulation (drug effects)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Hep G2 Cells
• Humans
• Liver Neoplasms (drug therapy, metabolism)
• Mice
• Mice, Inbred BALB C
• Mollusk Venoms (pharmacology)
• Peptides (pharmacology)