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Adjuvant and novel anti‐cancer drug, keyhole limpet hemocyanin, targets serotonin signaling pathway by inhibiting feeding, locomotion and egg laying in C. elegans
Author(s) -
Huggins Luke Graham,
Davis Linda Vona
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.748.13
Subject(s) - keyhole limpet hemocyanin , biology , adjuvant , signal transduction , caenorhabditis elegans , model organism , immune system , pharmacology , microbiology and biotechnology , immunology , biochemistry , gene
Keyhole limpet hemocyanin (KLH) is a copper‐containing respiratory pigment found in the mollusk, Megathura crenulata. Its primary biological role is the uptake, transport, and release of oxygen during respiration. KLH stimulates a host immune response making it suitable as an adjuvant for vaccines, and has been shown to inhibit cellular proliferation in human cancer cell lines of the breast, esophagus, pancreas, and prostate. Little is known about the physiological effects and molecular targets of this novel immunotherapy agent. To study the functional characterization of KLH, we selected Caenorhabditis elegans, a small, free‐living nematode worm frequently used as a genetic and developmental model organism. Worms were treated for 0–48 hours in liquid culture containing KLH (0–500 mg/mL), and scored for changes in feeding, locomotion, and egg‐laying behaviors. When treated with the drug KLH, there was a time and dose‐dependent decrease in feeding behavior and locomotion coupled with an increase in egg‐retention. All behaviors are regulated by serotonin signaling in C. elegans through a heterotrimeric G‐protein linked receptor pathway. These results suggest that the molecular actions of KLH target the serotonergic signaling pathway and warrant further validation as a novel therapeutic entry point in a disease model. Funded by NIH AI034544 and P20 RR16477.