Brassinin enhances the anticancer actions of paclitaxel by targeting multiple signaling pathways in colorectal cancer cells

Phytother Res. 2021 Jul;35(7):3875-3885. doi: 10.1002/ptr.7095. Epub 2021 Apr 1.

Abstract

Brassinin (BSN), a precursor of phytoalexins, extracted from Chinese cabbage has been reported to act as a promising anti-neoplastic agent. However, the effects of BSN on colon cancer cells and its underlying mechanisms have not been fully elucidated. This study aimed at investigating the anti-neoplastic impact of BSN and its possible synergistic effect with paclitaxel on colon cancer cells. The effect of BSN on Janus-activated kinases (JAKs)/signal transducer and activator of transcription 3 (STAT3) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathways and its downstream functions was deciphered using diverse assays in colon carcinoma cells. We found that BSN displayed significant cytotoxic effect and suppressed cell proliferation on colon carcinoma cells. Additionally, it was noted that BSN modulated oncogenic gene expression and induced apoptosis through down regulating multiple oncogenic signaling cascades such as JAKs/STAT3 and PI3K/Akt/mTOR simultaneously. Besides, BSN-paclitaxel combination significantly increased cytotoxicity and induced apoptosis synergistically as compared with individual treatment of both the agents. Overall, our findings indicate that BSN may be a novel candidate for anti-colon cancer targeted therapy.

Keywords: JAKs/STAT3; PI3K/Akt/mTOR; brassinin; colorectal cancer cells.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Colonic Neoplasms* / drug therapy
  • Humans
  • Indoles / pharmacology*
  • Paclitaxel* / pharmacology
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Signal Transduction / drug effects*
  • TOR Serine-Threonine Kinases
  • Thiocarbamates / pharmacology*

Substances

  • Indoles
  • Thiocarbamates
  • brassinin
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Paclitaxel