Rosmarinic acid suppresses inflammation, angiogenesis, and improves paclitaxel induced apoptosis in a breast cancer model via NF3 κB-p53-caspase-3 pathways modulation

J Appl Biomed. 2021 Dec;19(4):202-209. doi: 10.32725/jab.2021.024. Epub 2021 Oct 27.

Abstract

Rosmarinic acid is a natural polyphenolic compound that is found in different plant species and used for different medicinal purposes. This study aimed to investigate the chemo-preventive effect of rosmarinic acid and evaluate its antitumor efficacy alone or in combination with Paclitaxel in breast cancer mice model. Ehrlich induced mice mammary solid tumor model was used in the study. Mice were treated with oral rosmarinic acid and intraperitoneal Paclitaxel. Inflammation, angiogenesis, and apoptosis were checked. Enzyme linked immunosorbent assay (ELISA), quantitative real time PCR, and immunohistochemical methods were performed. Rosmarinic acid used prior to tumor induction suppressed NF-κB, TNF-α, vascular endothelial growth factor (VEGF) serum levels, and VEGF receptors. It also triggered apoptosis by restoring the levels of P53, Bcl-2, Bax, and caspase-3. Furthermore, in Ehrlich solid tumor mice, rosmarinic acid, and/or Paclitaxel significantly suppressed tumor growth with an increase in apoptotic markers P53 and Caspase-3 levels, and suppressed the Bcl2/Bax ratio. Rosmarinic acid exerted chemo-preventive and therapeutic potential alone or in combination with Paclitaxel. Moreover, rosmarinic acid targets numerous signaling pathways associated with breast cancer.

Keywords: Angiogenesis; Apoptosis; Breast cancer; Inflammation; Paclitaxel; Rosmarinic acid.

MeSH terms

  • Animals
  • Apoptosis
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / metabolism
  • Caspase 3 / drug effects
  • Caspase 3 / metabolism
  • Cinnamates* / pharmacology
  • Depsides* / pharmacology
  • Inflammation / drug therapy
  • Mice
  • NF-kappa B / drug effects
  • NF-kappa B / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Neovascularization, Pathologic / drug therapy
  • Paclitaxel* / pharmacology
  • Rosmarinic Acid
  • Tumor Suppressor Protein p53 / drug effects
  • Tumor Suppressor Protein p53 / metabolism
  • Vascular Endothelial Growth Factor A / metabolism
  • bcl-2-Associated X Protein / metabolism

Substances

  • Cinnamates
  • Depsides
  • NF-kappa B
  • Tumor Suppressor Protein p53
  • Vascular Endothelial Growth Factor A
  • bcl-2-Associated X Protein
  • Caspase 3
  • Paclitaxel