Evaluation of neurotoxicity of anticancer drugs using nematode <i>Caenorhabditis elegans</i> as a model organism

Abstract

It is well established that platinum-based drugs, including oxaliplatin (L-OHP) and cisplatin (CDDP), as well as microtubule inhibitors paclitaxel (PTX) and vincristine (VCR), are associated with chemotherapy-induced peripheral neuropathy (CIPN). In this study, we examined and compared the characteristics of neuropathies induced by L-OHP, CDDP, PTX, and VCR to evaluate whether Caenorhabditis elegans (C. elegans) could serve as a model organism for human CIPN. Worms were cultured on nematode growth medium plates, and L1 larvae synchronized by gel filtration were employed. We then performed bioassays and examined motility. In the motility test, exposure was performed for 2, 24, and 48 hr, and time-dependent effects were measured for each exposure time and 24 hr after terminating exposure. Herein, we observed that L-OHP and CDDP exerted concentration-dependent effects above a certain concentration, and PTX and VCR exerted concentration-dependent negative effects in the bioassay. Motility recovered in L-OHP-, PTX-, and VCR-treated worms on terminating exposure. However, CDDP exposure tended to reduce motility even 24 hr after terminating exposure. L-OHP exposure could decrease motility 2 hr after exposure, with a trend toward recovery 24 hr after terminating drug exposure. The findings of the present study revealed that C. elegans could exhibit neuropathy characteristics suggested to be similar to those observed in humans, indicating that this organism could be a suitable model to explore human CIPN.

Exploring the Potential of Lapatinib, Fulvestrant, and Paclitaxel Conjugated with Glycidylated PAMAM G4 Dendrimers for Cancer and Parasite Treatment

“…The small size, ease of handling, and possibility of genetic modification of C. elegans provide a sophisticated in vivo platform that combines the technical advantages of a microorganism with the greater biological complexity of a multicellular organism [55,56]. C. elegans has been used successfully to test the activity of EGFR tyrosine kinase inhibitors [57], selective estrogen receptor degraders (SERDs) [58], and microtubule-stabilizing drugs [59]; therefore, the biological activity of the synthesized constructs was studied also in vivo on C. elegans. Additionally, its usefulness as a model for mixture toxicity testing was confirmed [60].…”