Phenoxodiol protects against Cisplatin induced neurite toxicity in a PC-12 cell model.
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 microM showed no cytotoxicity and blocked the Cisplatin induced neurite toxicity, while phenoxodiol at 10 microM 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.


CONCLUSIONS
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.
Centre for Neuroscience, The University of Melbourne, Parkville, Victoria, Australia. rklein@unimelb.edu.au <rklein@unimelb.edu.au>
Reuben
R
Klein
David
D
Brown
Ann M
AM
Turnley
D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors / Q000633:toxicity; D002945:Cisplatin / Q000037:antagonists & inhibitors* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D007529:Isoflavones / Q000494:pharmacology* / Q000627:therapeutic use; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity; D016716:PC12 Cells; D010525:Peripheral Nerves / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D051381:Rats; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology
D000970:Antineoplastic Agents; D007529:Isoflavones; D018696:Neuroprotective Agents; D009498:Neurotoxins; C471183:phenoxodiol; D002945:Cisplatin