Back to Search
Start Over
Astragalus Polysaccharide RAP Selectively Attenuates Paclitaxel-Induced Cytotoxicity Toward RAW 264.7 Cells by Reversing Cell Cycle Arrest and Apoptosis.
- Source :
- Frontiers in Pharmacology; 2/11/2019, pN.PAG-N.PAG, 9p
- Publication Year :
- 2019
-
Abstract
- 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-H<subscript>2</subscript>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 Taxol-induced toxicity, by changing the cell cycle and apoptosis. [ABSTRACT FROM AUTHOR]
- Subjects :
- ANKLEBONE
POLYSACCHARIDES
PACLITAXEL
CELL cycle
APOPTOSIS
Subjects
Details
- Language :
- English
- ISSN :
- 16639812
- Database :
- Complementary Index
- Journal :
- Frontiers in Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 134644263
- Full Text :
- https://doi.org/10.3389/fphar.2018.01580