Baicalin; a promising chemopreventive agent, enhances the antitumor effect of 5-FU against breast cancer and inhibits tumor growth and angiogenesis in Ehrlich solid tumor

Biomed Pharmacother. 2022 Feb:146:112599. doi: 10.1016/j.biopha.2021.112599. Epub 2021 Dec 27.

Abstract

Despite considerable advances in cancer treatment, chemotherapy remains a cornerstone in breast cancer therapy. Therefore, reducing chemoresistance and adverse effects of chemotherapy is a priority. In this regard, Baicalin (BA) is the dominant natural flavonoid extracted from the roots of Scutellaria baicalensis showed fascinating antitumor activity in many types of cancers, including breast cancer. The present study aimed to explore the chemopreventive and antitumor action of baicalin alone and in combination with 5-FU in addition to its ability to enhance the antitumor effect of 5-FU on breast cancer using the Ehrlich solid tumor-mice model.

Materials and methods: A total of 70 female mice were divided into seven groups (1st group, saline group; 2nd group, DMSO group; 3rd group, BA+EST group; 4th group, EST group; 5th group, EST+5-FU; 6th group, EST+BA group; 7th group, EST+5-FU+BA).tumors were assessed by weight and histopathological examination. Inflammation, angiogenesis, and apoptosis were examined by ELISA, qRT-PCR, and immunohistochemical examinations.

Results: showed that pre-treatment with baicalin and treatment with baicalin and/or 5-FU significantly reduced inflammation and angiogenesis indicated by suppression of NF-kB/ IL-1β and VEGF amplification loop with marked elevation in apoptosis indicated by up-regulation of apoptotic caspase-3, pro-apoptotic p53, Bax and downregulation of anti-apoptotic Bcl-2.

Conclusion: BA is a promising preventive or adjuvant therapy in breast cancer treatment with 5-FU mainly via cooperative inhibition of inflammation, angiogenesis, and triggering apoptotic cell death.

Keywords: 5-Fluorouracil; Angiogenesis; Apoptosis; Baicalin; Breast cancer; Ehrlich solid tumor.

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols
  • Breast Neoplasms / pathology*
  • Disease Models, Animal
  • Drug Synergism
  • Female
  • Flavonoids / pharmacology*
  • Fluorouracil / pharmacology*
  • Inflammation Mediators / metabolism
  • Mice
  • Neovascularization, Pathologic / metabolism
  • Tumor Burden
  • Vascular Endothelial Growth Factor A / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Flavonoids
  • Inflammation Mediators
  • Vascular Endothelial Growth Factor A
  • baicalin
  • Fluorouracil