Author:
Klein Reuben,Brown David,Turnley Ann M
Abstract
Abstract
Background
Many commonly used chemotherapeutic agents, such as Cisplatin, are restricted in their potential anti-neoplastic effectiveness by their side effects, with one of the most problematic being induction of peripheral neuropathy. Although a number of different neurotrophic, neuroprotective or anti-oxidant treatments have been tried in order to prevent or treat the neuropathies, to date they have met with limited success. Phenoxodiol is a new chemotherapeutic agent that has anti-proliferative and apoptotic effects on a range of cancer cells. PC12 cells are a commonly used neuronal cell model for examination of neurite outgrowth. In this study we examined whether phenoxodiol could protect against Cisplatin induced neurite inhibition in PC12 cells as an indication of the potential to protect against neuropathy.
Results
Using the PC12 neuronal cell line, concentrations of Cisplatin were chosen that induced moderate or strong neurite toxicity within 24 hrs but were not cytotoxic. The effect of Phenoxodiol on Cisplatin induced neurite toxicity was assessed by measurement of neurite outgrowth. Addition of phenoxodiol at 100 nM or 1 μM showed no cytotoxicity and blocked the Cisplatin induced neurite toxicity, while phenoxodiol at 10 μM was cytotoxic and enhanced neurite toxicity of Cisplatin. When Cisplatin was added for 24 hrs, then washed out and the cells allowed to recover for 48 hrs, neurite outgrowth was not restored and addition of phenoxodiol did not further promote recovery or restore the Cisplatin treated cells.
Conclusion
In addition to its potential as a chemotherapeutic agent Phenoxodiol may thus also have the potential to be used in conjunction with Cisplatin chemotherapy to prevent induction of neuropathy.
Publisher
Springer Science and Business Media LLC
Subject
Cellular and Molecular Neuroscience,General Neuroscience
Reference37 articles.
1. Quasthoff S, Hartung HP: Chemotherapy-induced peripheral neuropathy. J Neurol. 2002, 249 (1): 9-17. 10.1007/PL00007853.
2. Huang H, Zhu L, Reid BR, Drobny GP, Hopkins PB: Solution structure of a cisplatin-induced DNA interstrand cross-link. Science. 1995, 270 (5243): 1842-1845. 10.1126/science.270.5243.1842.
3. Ta LE, Espeset L, Podratz J, Windebank AJ: Neurotoxicity of oxaliplatin and cisplatin for dorsal root ganglion neurons correlates with platinum-DNA binding. Neurotoxicology. 2006, 992-1002. 10.1016/j.neuro.2006.04.010.
4. Apfel SC, Arezzo JC, Lipson L, Kessler JA: Nerve growth factor prevents experimental cisplatin neuropathy. Ann Neurol. 1992, 31 (1): 76-80. 10.1002/ana.410310114.
5. Hayakawa K, Itoh T, Niwa H, Mutoh T, Sobue G: NGF prevention of neurotoxicity induced by cisplatin, vincristine and taxol depends on toxicity of each drug and NGF treatment schedule: in vitro study of adult rat sympathetic ganglion explants. Brain Res. 1998, 794 (2): 313-319. 10.1016/S0006-8993(98)00305-9.
Cited by
19 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献