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Astragalus Polysaccharide RAP Selectively Attenuates Paclitaxel-Induced Cytotoxicity Toward RAW 264.7 Cells by Reversing Cell Cycle Arrest and Apoptosis
Bao, WR1; Li, ZP1; Zhang, QW1; Li, LF1; Liu, HB1; Ma, DL2; Leung, CH3; Lu, AP1; Bian, Z1; Han, QB1
2019
Source PublicationFRONTIERS IN PHARMACOLOGY
ISSN1663-9812
Volume9
AbstractPurpose: 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-H(2)A, 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 Taxolinduced toxicity, by changing the cell cycle and apoptosis.
KeywordCell Cycle Astragalus Polysaccharide Cytotoxicity Protective Effect Apoptosis
DOI10.3389/fphar.2018.01580
Indexed BySCI
Language英语
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000458238700001
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Cited Times [WOS]:1   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorBian, Z
Affiliation1.Hong Kong Baptist Univ, Sch Chinese Med, Kowloon Tong, Hong Kong, Peoples R China
2.Hong Kong Baptist Univ, Dept Chem, Kowloon Tong, Hong Kong, Peoples R China
3.University of Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau, Peoples R China
Recommended Citation
GB/T 7714
Bao, WR,Li, ZP,Zhang, QW,et al. Astragalus Polysaccharide RAP Selectively Attenuates Paclitaxel-Induced Cytotoxicity Toward RAW 264.7 Cells by Reversing Cell Cycle Arrest and Apoptosis[J]. FRONTIERS IN PHARMACOLOGY,2019,9.
APA Bao, WR.,Li, ZP.,Zhang, QW.,Li, LF.,Liu, HB.,...&Han, QB.(2019).Astragalus Polysaccharide RAP Selectively Attenuates Paclitaxel-Induced Cytotoxicity Toward RAW 264.7 Cells by Reversing Cell Cycle Arrest and Apoptosis.FRONTIERS IN PHARMACOLOGY,9.
MLA Bao, WR,et al."Astragalus Polysaccharide RAP Selectively Attenuates Paclitaxel-Induced Cytotoxicity Toward RAW 264.7 Cells by Reversing Cell Cycle Arrest and Apoptosis".FRONTIERS IN PHARMACOLOGY 9(2019).
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