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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2018.01580

Astragalus polysaccharide RAP selectively attenuates paclitaxel-induced cytotoxicity towards RAW 264.7 cells by reversing cell cycle arrest and apoptosis

Wan-Rong Bao1, Zhi-Peng Li1, Quan-Wei Zhang1, Li-Feng Li1, Hong-Bing Liu1,  Dik-Lung Ma2, Chung-Hang Leung3,  Aiping Lu1, Zhao-Xiang Bian1* and  Quan-Bin Han4*
  • 1School of Chinese Medicine, Hong Kong Baptist University, China
  • 2Department of Chemistry, Hong Kong Baptist University, China
  • 3University of Macau, China
  • 4Hong Kong Baptist University, Hong Kong

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 series 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. We injected one group with Taxol and one group with Taxol+ RAP, and recorded differences in the life spans of the mice. 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 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 and 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 G2/M phase arrest and protected cells from apoptosis. Taxol up-regulated the levels of Caspase-3, P-H2A, PARP, Chk1, p53 and p21 and down-regulated Bcl-Xl and Mcl-1, and RAP reversed the expression of all these proteins.

Conclusions: These results suggested that RAP can protect immune cells from Taxol-induced toxicity, by changing the cell cycle and apoptosis.

Keywords: Astragalus polysaccharide, Cytotoxicity, protective effect, Cell Cycle, Apoptosis

Received: 31 Jul 2018; Accepted: 31 Dec 2018.

Edited by:

Stephen Cho Wing SZE, Hong Kong Baptist University, Hong Kong

Reviewed by:

Anna-Mart Engelbrecht, Stellenbosch University, South Africa
PUI KEI WU, Medical College of Wisconsin, United States  

Copyright: © 2018 Bao, Li, Zhang, Li, Liu, Ma, Leung, Lu, Bian and Han. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Zhao-Xiang Bian, School of Chinese Medicine, Hong Kong Baptist University, HongKong, China,
Dr. Quan-Bin Han, Hong Kong Baptist University, Kowloon, Hong Kong,