scholarly journals Induction of Neurite Outgrowth in PC12 Cells by α-Phenyl-N-tert-butylnitron through Activation of Protein Kinase C and the Ras-Extracellular Signal-regulated Kinase Pathway

2001 ◽  
Vol 276 (35) ◽  
pp. 32779-32785 ◽  
Author(s):  
Masahisa Tsuji ◽  
Osamu Inanami ◽  
Mikinori Kuwabara
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Neurite Outgrowth ◽  
Pc12 Cells ◽  
Extracellular Signal Regulated Kinase ◽  
Kinase C ◽  
Extracellular Signal ◽  
Kinase Pathway

scholarly journals Tamoxifen suppresses paclitaxel-, vincristine-, and bortezomib-induced neuropathy via inhibition of the protein kinase C/extracellular signal-regulated kinase pathway

Tumor Biology ◽  
2018 ◽  
Vol 40 (10) ◽  
pp. 101042831880867 ◽  
Author(s):  
Masanobu Tsubaki ◽  
Tomoya Takeda ◽  
Mikihiro Matsumoto ◽  
Natsuki Kato ◽  
Shota Yasuhara ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Dorsal Root ◽  
Extracellular Signal Regulated Kinase ◽  
Chemotherapy Drugs ◽  
Kinase C ◽  
Extracellular Signal ◽  
Chemotherapy Agents ◽  
Kinase Pathway

Chemotherapy-induced neuropathy is a highly problematic, dose-limiting effect of potentially curative regimens of cancer chemotherapy. When neuropathic pain is severe, patients often either switch to less-effective chemotherapy agents or choose to discontinue chemotherapy entirely. Conventional chemotherapy drugs used to treat lung and breast cancer, multiple myeloma, and lymphoma include paclitaxel, vincristine, and bortezomib. Approximately 68% of patients receiving these anticancer drugs develop neuropathy within the first month of treatment, and while strategies to prevent chemotherapy-induced neuropathy have been investigated, none have yet been proven as effective. Recent reports suggest that chemotherapy-induced neuropathy is associated with signal transduction molecules, including protein kinase C and mitogen-activated protein kinases. It is currently unclear whether protein kinase C inhibition can prevent chemotherapy-induced neuropathy. In this study, we found that tamoxifen, a protein kinase C inhibitor, suppressed paclitaxel-, vincristine-, and bortezomib-induced cold and mechanical allodynia in mice. In addition, chemotherapy drugs induce neuropathy via the protein kinase C/extracellular signal-regulated kinase pathway in the spinal cord in lumbar segments 4–6 and dorsal root ganglions. In addition, tamoxifen was shown to act synergistically with paclitaxel to inhibit tumor-growth in mice injected with tumor cells. Our results indicated that paclitaxel-, vincristine-, and bortezomib-induced neuropathies were associated with the protein kinase C/extracellular signal-regulated kinase pathway in the lumbar spinal cord and dorsal root ganglions, which suggest that protein kinase C inhibitors may be therapeutically effective for the prevention of chemotherapy-induced neuropathy when administered with standard chemotherapy agents.

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