Kamishoyosan and Shakuyakukanzoto promote recovery from paclitaxel-induced neurite retraction in PC12 cells
Abstract Background In chemotherapy, the full round of treatment must be completed as scheduled to achieve the strongest therapeutic effect. However, peripheral neuropathy, a severe side effect of the chemotherapeutic agent paclitaxel, can force the premature discontinuation of treatment. As some ka...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-07-01
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| Series: | Journal of Pharmaceutical Health Care and Sciences |
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| Online Access: | http://link.springer.com/article/10.1186/s40780-017-0090-y |
| _version_ | 1818571209572352000 |
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| author | Ken Konaka Kota Moriyama Takumi Sakurada Naoto Okada Masaki Imanishi Yoshito Zamami Kazuyoshi Kawazoe Shuji Fushitani Keisuke Ishizawa |
| author_facet | Ken Konaka Kota Moriyama Takumi Sakurada Naoto Okada Masaki Imanishi Yoshito Zamami Kazuyoshi Kawazoe Shuji Fushitani Keisuke Ishizawa |
| author_sort | Ken Konaka |
| collection | DOAJ |
| description | Abstract Background In chemotherapy, the full round of treatment must be completed as scheduled to achieve the strongest therapeutic effect. However, peripheral neuropathy, a severe side effect of the chemotherapeutic agent paclitaxel, can force the premature discontinuation of treatment. As some kampo practitioners have suggested that it may be possible to counteract such side effects, we analyzed the effects of Kamishoyosan, Shakuyakukanzoto, and Goshajinkigan in an in vitro model of paclitaxel-induced peripheral neuropathy. Methods Paclitaxel-treated PC12 cells were assessed for neurite length and performed Western blot analysis for growth-associated protein-43 (GAP-43) and light neurofilament protein (NF-L) levels in the presence of nerve growth factor (NGF); they were re-assessed, with additional testing for acetylcholinesterase levels, after application of one of the kampo. We also compared phosphorylation of extracellular signal-regulated kinase (Erk)1/2 and Akt via Western blot analysis. About effect of kampo to anticancer efficacy, we confirmed cell cytotoxicity in A549 cells using MTT assay. Results Addition of Kamishoyosan or Shakuyakukanzoto, but not Goshajinkigan, significantly improved neurite length and GAP-43 and NF-L levels from paclitaxel-treated PC12 cells, relative to those of only NGF-treated PC12 cells. The promoting effect of Kamishoyosan and Shakuyakukanzoto in neurite outgrowth is confirmed when NGF promoted neurite outgrowth, and it was inhibited partially when Erk1/2 and Akt were blocked by Erk1/2 inhibitor or Akt inhibitor alone. Furthermore, neurite outgrowth induced by TJ24 and TJ68 was inhibited more strongly when Erk1/2 inhibitor and Akt inhibitor were treated at the same time. NGF with Kamishoyosan or Shakuyakukanzoto promoted the proportion of phosphorylated Erk1/2 and phosphorylated Akt compare with NGF only. On the other hand, Kamishoyosan or Shakuyakukanzoto didn’t influence cytotoxicity of paclitaxel in A549 cells. Conclusions Kamishoyosan or Shakuyakukanzoto promotes neurite outgrowth with NGF via increasing the proportion of phosphorylated Erk1/2 and phosphorylated Akt in PC12 cells. The effect applies to recovery from paclitaxel-induced axonal involvement and might promote recovery from paclitaxel-induced neuropathy without influence of anticancer effect of paclitaxel. |
| first_indexed | 2024-12-14T13:52:47Z |
| format | Article |
| id | doaj.art-b7c6b4193009430ab7d57fd15031ec2f |
| institution | Directory Open Access Journal |
| issn | 2055-0294 |
| language | English |
| last_indexed | 2024-12-14T13:52:47Z |
| publishDate | 2017-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Pharmaceutical Health Care and Sciences |
| spelling | doaj.art-b7c6b4193009430ab7d57fd15031ec2f2022-12-21T22:58:59ZengBMCJournal of Pharmaceutical Health Care and Sciences2055-02942017-07-01311810.1186/s40780-017-0090-yKamishoyosan and Shakuyakukanzoto promote recovery from paclitaxel-induced neurite retraction in PC12 cellsKen Konaka0Kota Moriyama1Takumi Sakurada2Naoto Okada3Masaki Imanishi4Yoshito Zamami5Kazuyoshi Kawazoe6Shuji Fushitani7Keisuke Ishizawa8Department of Pharmacy, Tokushima Municipal HospitalDepartment of Pharmacy, Shimane University HospitalDepartment of Pharmacy, Tokushima University HospitalDepartment of Pharmacy, Tokushima University HospitalDepartment of Pharmacy, Tokushima University HospitalDepartment of Pharmacy, Tokushima University HospitalDepartment of Clinical Pharmacy Practice Pedagogy Institute of Biomedical Sciences, Tokushima University Graduate SchoolDepartment of Pharmacy, Tokushima Municipal HospitalDepartment of Pharmacy, Tokushima University HospitalAbstract Background In chemotherapy, the full round of treatment must be completed as scheduled to achieve the strongest therapeutic effect. However, peripheral neuropathy, a severe side effect of the chemotherapeutic agent paclitaxel, can force the premature discontinuation of treatment. As some kampo practitioners have suggested that it may be possible to counteract such side effects, we analyzed the effects of Kamishoyosan, Shakuyakukanzoto, and Goshajinkigan in an in vitro model of paclitaxel-induced peripheral neuropathy. Methods Paclitaxel-treated PC12 cells were assessed for neurite length and performed Western blot analysis for growth-associated protein-43 (GAP-43) and light neurofilament protein (NF-L) levels in the presence of nerve growth factor (NGF); they were re-assessed, with additional testing for acetylcholinesterase levels, after application of one of the kampo. We also compared phosphorylation of extracellular signal-regulated kinase (Erk)1/2 and Akt via Western blot analysis. About effect of kampo to anticancer efficacy, we confirmed cell cytotoxicity in A549 cells using MTT assay. Results Addition of Kamishoyosan or Shakuyakukanzoto, but not Goshajinkigan, significantly improved neurite length and GAP-43 and NF-L levels from paclitaxel-treated PC12 cells, relative to those of only NGF-treated PC12 cells. The promoting effect of Kamishoyosan and Shakuyakukanzoto in neurite outgrowth is confirmed when NGF promoted neurite outgrowth, and it was inhibited partially when Erk1/2 and Akt were blocked by Erk1/2 inhibitor or Akt inhibitor alone. Furthermore, neurite outgrowth induced by TJ24 and TJ68 was inhibited more strongly when Erk1/2 inhibitor and Akt inhibitor were treated at the same time. NGF with Kamishoyosan or Shakuyakukanzoto promoted the proportion of phosphorylated Erk1/2 and phosphorylated Akt compare with NGF only. On the other hand, Kamishoyosan or Shakuyakukanzoto didn’t influence cytotoxicity of paclitaxel in A549 cells. Conclusions Kamishoyosan or Shakuyakukanzoto promotes neurite outgrowth with NGF via increasing the proportion of phosphorylated Erk1/2 and phosphorylated Akt in PC12 cells. The effect applies to recovery from paclitaxel-induced axonal involvement and might promote recovery from paclitaxel-induced neuropathy without influence of anticancer effect of paclitaxel.http://link.springer.com/article/10.1186/s40780-017-0090-yPaclitaxelNeuropathyKamishoyosanShakuyakukanzotoPC12 cells |
| spellingShingle | Ken Konaka Kota Moriyama Takumi Sakurada Naoto Okada Masaki Imanishi Yoshito Zamami Kazuyoshi Kawazoe Shuji Fushitani Keisuke Ishizawa Kamishoyosan and Shakuyakukanzoto promote recovery from paclitaxel-induced neurite retraction in PC12 cells Journal of Pharmaceutical Health Care and Sciences Paclitaxel Neuropathy Kamishoyosan Shakuyakukanzoto PC12 cells |
| title | Kamishoyosan and Shakuyakukanzoto promote recovery from paclitaxel-induced neurite retraction in PC12 cells |
| title_full | Kamishoyosan and Shakuyakukanzoto promote recovery from paclitaxel-induced neurite retraction in PC12 cells |
| title_fullStr | Kamishoyosan and Shakuyakukanzoto promote recovery from paclitaxel-induced neurite retraction in PC12 cells |
| title_full_unstemmed | Kamishoyosan and Shakuyakukanzoto promote recovery from paclitaxel-induced neurite retraction in PC12 cells |
| title_short | Kamishoyosan and Shakuyakukanzoto promote recovery from paclitaxel-induced neurite retraction in PC12 cells |
| title_sort | kamishoyosan and shakuyakukanzoto promote recovery from paclitaxel induced neurite retraction in pc12 cells |
| topic | Paclitaxel Neuropathy Kamishoyosan Shakuyakukanzoto PC12 cells |
| url | http://link.springer.com/article/10.1186/s40780-017-0090-y |
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