Oxaliplatin-based regimens are effective in metastasized advanced
cancers. However, a major limitation to their widespread use is represented by neurotoxicity that leads to
peripheral neuropathy. In this study we evaluated the roles of a proven immunotherapeutic agent [Gc-
protein-derived macrophage activating factor (
GcMAF)] in preventing or decreasing
oxaliplatin-induced neuronal damage and in modulating microglia activation following
oxaliplatin-induced damage. The effects of
oxaliplatin and of a commercially available formula of
GcMAF [
oleic acid-
GcMAF (OA-
GcMAF)] were studied in human neurons (SH-SY5Y cells) and in human microglial cells (C13NJ). Cell density, morphology and viability, as well as production of cAMP and expression of
vascular endothelial growth factor (
VEGF), markers of neuron regeneration [
neuromodulin or growth associated protein-43 (Gap-43)] and markers of microglia activation [ionized
calcium binding adaptor molecule 1 (Iba1) and B7-2], were determined. OA-
GcMAF reverted the damage inflicted by
oxaliplatin on human neurons and preserved their viability. The
neuroprotective effect was accompanied by increased intracellular cAMP production, as well as by increased expression of
VEGF and
neuromodulin. OA-
GcMAF did not revert the effects of
oxaliplatin on microglial cell viability. However, it increased microglial activation following
oxaliplatin-induced damage, resulting in an increased expression of the markers Iba1 and B7-2 without any concomitant increase in cell number. When neurons and microglial cells were co-cultured, the presence of OA-
GcMAF significantly counteracted the toxic effects of
oxaliplatin. Our results demonstrate that OA-
GcMAF, already used in the
immunotherapy of advanced
cancers, may significantly contribute to neutralizing the neurotoxicity induced by
oxaliplatin, at the same time possibly concurring to an integrated anticancer effect. The association between these two powerful anticancer molecules would probably produce the dual effect of reduction of
oxaliplatin-induced neurotoxicity, together with possible synergism in the overall anticancer effect.