Astaxanthin Inhibits PC-3 Xenograft Prostate Tumor Growth in Nude Mice

Mar Drugs. 2017 Mar 8;15(3):66. doi: 10.3390/md15030066.

Abstract

Prostate cancer (PCa), the most common malignancy in men, is a major cause of cancer deaths. A better understanding of the mechanisms that drive tumor initiation and progression may identify actionable targets to improve treatment of this patient group. As a dietary carotenoid, astaxanthin has been demonstrated to exert beneficial effects against inflammation, cardiovascular disease, oxidative damage, or different cancer sites. This study used intragastric administration of astaxanthin to detect its role on tumor proliferation, apoptosis, microRNA (miRNA) overexpression, and microbacteria composition change by establishing androgen-independent PCa cell PC-3 xenograft nude mice. Nude mice were inoculated with androgen-independent prostate cancer PC-3 cells subcutaneously. The intervention was started when tumors reached 0.5-0.6 cm in diameter. Mice were intragastrically administered 100 mg/kg astaxanthin (HA), 25 mg/kg astaxanthin (LA), or olive oil (TC). The results showed that 100 mg/kg astaxanthin significantly inhibited tumor growth compared to the TC group, with an inhibitory rate of 41.7%. A decrease of Ki67 and proliferating cell nuclear antigen (PCNA) as well as an increase of cleaved caspase-3 were observed in HA-treated tumors, along with increasing apoptotic cells, obtained by TUNEL assay. The HA significantly elevated the levels of tumor suppressors miR-375 and miR-487b in tumor tissues and the amount of Lactobacillus sp. and Lachnospiraceae in mice stools, while there was no significant difference between LA and TC groups. These results provide a promising regimen to enhance the therapeutic effect in a dietary supplement manner.

Keywords: PCR-DGGE; astaxanthin; immunohistochemistry; miRNA; prostate cancer.

MeSH terms

  • Androgens / metabolism
  • Animals
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism
  • Transplantation, Heterologous / methods
  • Xanthophylls / pharmacology
  • Xenograft Model Antitumor Assays / methods

Substances

  • Androgens
  • Xanthophylls
  • astaxanthine
  • Caspase 3