Format

Send to

Choose Destination
Sci Rep. 2017 Nov 15;7(1):15624. doi: 10.1038/s41598-017-15934-0.

A standardized herbal extract mitigates tumor inflammation and augments chemotherapy effect of docetaxel in prostate cancer.

Author information

1
Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
2
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
3
Bioinformatics and Biostatistics Core, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan.
4
Institute of Biotechnology, National Taiwan University, Taipei, Taiwan.
5
Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan. pwhsiao@gate.sinica.edu.tw.
6
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan. pwhsiao@gate.sinica.edu.tw.

Abstract

Activation of the NFκB pathway is often associated with advanced cancer and has thus been regarded as a rational therapeutic target. Wedelia chinensis is rich in luteolin, apigenin, and wedelolactone that act synergistically to suppress androgen receptor activity in prostate cancer. Interestingly, our evaluation of a standardized Wedelia chinensis herbal extract (WCE) concluded its efficacy on hormone-refractory prostate cancer through systemic mechanisms. Oral administration of WCE significantly attenuated tumor growth and metastasis in orthotopic PC-3 and DU145 xenografts. Genome-wide transcriptome analysis of these tumors revealed that WCE suppressed the expression of IKKα/β phosphorylation and downstream cytokines/chemokines, e.g., IL6, CXCL1, and CXCL8. Through restraining the cytokines expression, WCE reduced tumor-elicited infiltration of myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs) and endothelial cells into the tumors, therefore inhibiting angiogenesis, tumor growth, and metastasis. In MDSCs, WCE also reduced STAT3 activation, downregulated S100A8 expression and prevented their expansion. Use of WCE in combination with docetaxel significantly suppressed docetaxel-induced NFκB activation, boosted the therapeutic effect and reduced the systemic toxicity caused by docetaxel monotherapy. These data suggest that a standardized preparation of Wedelia chinensis extract improved prostate cancer therapy through immunomodulation and has potential application as an adjuvant agent for castration-resistant prostate cancer.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center