Astragalus Polysaccharide RAP Selectively Attenuates Paclitaxel-Induced Cytotoxicity Toward RAW 264.7 Cells by Reversing Cell Cycle Arrest and Apoptosis
Purpose: The purpose of this study was to determine if an Astragalus polysaccharide (RAP) can protect immune cells from the toxic side effects of paclitaxel (Taxol), a powerful anti-tumor drug whose equally powerful side effects limit its clinical use. Methods: We hypothesized that RAP can reduce the toxic effects induced by Taxol. To test this hypothesis, we conducted a series of studies in vivo and in vitro. First, we confirmed RAP's effects in vivo utilizing BALB/c mice inoculated with 4T1 mouse breast cancer cells as the tumor model. Mice were treated with RAP and/or Taxol, and the differences in the life spans were recorded. Second, a co-culture cell model was used to study the protective effect of RAP on cells vis-a-vis Taxol. The cell cycle and apoptosis of RAW 264.7 cells that were treated with RAP with/without Taxol were checked by flow cytometry and Hoechst staining. Proteins involved in the cell cycle and apoptosis were also tested by Western blot to reveal the probable mechanism. Results: RAP prolonged the life span of tumor-bearing mice treated with Taxol. The in vitro experiments showed that Taxol suppressed the proliferation of RAW 264.7 cells while RAP protected the RAW 264.7 cells from Taxol-induced suppression. The protection is selective because RAP had no effect on 4T1 cells. Furthermore, Taxol clearly led to cell cycle arrest mainly at the G2/M phase and generated cytotoxicity against RAW 264.7 cells, while RAP blocked cell cycle arrest and protected cells from apoptosis. Taxol up-regulated the protein levels of P-H2A, PARP, Chk1, p53, and p21 and down-regulated Bcl-Xl and Mcl-1, and RAP reversed the expression of all these proteins. Conclusion: These results suggested that RAP can protect immune cells from Taxol-induced toxicity, by changing the cell cycle and apoptosis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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| Enthalten in: |
Frontiers in pharmacology - 9(2018) vom: 25., Seite 1580 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bao, Wan-Rong [VerfasserIn] |
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| Links: |
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| Themen: |
Apoptosis |
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| Anmerkungen: |
Date Revised 05.10.2023 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3389/fphar.2018.01580 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM294295887 |
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| 245 | 1 | 0 | |a Astragalus Polysaccharide RAP Selectively Attenuates Paclitaxel-Induced Cytotoxicity Toward RAW 264.7 Cells by Reversing Cell Cycle Arrest and Apoptosis |
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| 520 | |a Purpose: The purpose of this study was to determine if an Astragalus polysaccharide (RAP) can protect immune cells from the toxic side effects of paclitaxel (Taxol), a powerful anti-tumor drug whose equally powerful side effects limit its clinical use. Methods: We hypothesized that RAP can reduce the toxic effects induced by Taxol. To test this hypothesis, we conducted a series of studies in vivo and in vitro. First, we confirmed RAP's effects in vivo utilizing BALB/c mice inoculated with 4T1 mouse breast cancer cells as the tumor model. Mice were treated with RAP and/or Taxol, and the differences in the life spans were recorded. Second, a co-culture cell model was used to study the protective effect of RAP on cells vis-a-vis Taxol. The cell cycle and apoptosis of RAW 264.7 cells that were treated with RAP with/without Taxol were checked by flow cytometry and Hoechst staining. Proteins involved in the cell cycle and apoptosis were also tested by Western blot to reveal the probable mechanism. Results: RAP prolonged the life span of tumor-bearing mice treated with Taxol. The in vitro experiments showed that Taxol suppressed the proliferation of RAW 264.7 cells while RAP protected the RAW 264.7 cells from Taxol-induced suppression. The protection is selective because RAP had no effect on 4T1 cells. Furthermore, Taxol clearly led to cell cycle arrest mainly at the G2/M phase and generated cytotoxicity against RAW 264.7 cells, while RAP blocked cell cycle arrest and protected cells from apoptosis. Taxol up-regulated the protein levels of P-H2A, PARP, Chk1, p53, and p21 and down-regulated Bcl-Xl and Mcl-1, and RAP reversed the expression of all these proteins. Conclusion: These results suggested that RAP can protect immune cells from Taxol-induced toxicity, by changing the cell cycle and apoptosis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Astragalus polysaccharide | |
| 650 | 4 | |a apoptosis | |
| 650 | 4 | |a cell cycle | |
| 650 | 4 | |a cytotoxicity | |
| 650 | 4 | |a protective effect | |
| 700 | 1 | |a Li, Zhi-Peng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Quan-Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Li-Feng |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Hong-Bing |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Dik-Lung |e verfasserin |4 aut | |
| 700 | 1 | |a Leung, Chung-Hang |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Ai-Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Bian, Zhao-Xiang |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Quan-Bin |e verfasserin |4 aut | |
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