BRM270 Suppresses Cervical Cancer Stem Cell Characteristics and Progression by Inhibiting SOX2

In Vivo. 2020 May-Jun;34(3):1085-1094. doi: 10.21873/invivo.11879.

Abstract

Background/aim: Cervical cancer is one of the leading causes of cancer death in women worldwide. BRM270 (BRMLife) has therapeutic potential for cancer treatment owing to its ability to inhibit cell proliferation, and expression of cluster of differentiation (CD) 133 in CD133+ cancer cells. This study was designed to evaluate the therapeutic effects of plant extract formulation BRM270 against cervical cancer progression.

Materials and methods: The expression of sex-determining region Y-box 2 (SOX2) was tested in four different cervical cancer cell lines, HeLA, SiHa, Caski and C33A. SOX2-expressing SiHa and C33A cell lines were selected for further experiments on the in vitro and in vivo effects of BRM270 on cervical cancer progression using western blotting, flow cytometry, sphere-formation assay, magnetic-activated cell sorting of CD133+ cervical cancer cells, and xenografts in female athymic BALB/c nude mice.

Results: In the present study, in cervical cancer stem cells (CSCs), we found that BRM270 inhibited expression of SOX2, which is associated with cervical cancer initiation and metastasis. BRM270 also inhibited CD133 expression and induced apoptosis of CSCs and suppressed CD133+ CSC proliferation and sphere formation in vitro as well as SiHa and C33A cell xenograft tumor growth in vivo. This was accompanied by down-regulation of markers of epithelial-to-mesenchymal transition.

Conclusion: BRM270 might be an effective agent for cervical cancer treatment.

Keywords: BRM270; SOX2; cancer stem cells; cervical cancer; epithelial-to-mesenchymal transition.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Drugs, Chinese Herbal / pharmacology*
  • Epithelial-Mesenchymal Transition / drug effects
  • Female
  • Humans
  • Mice
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • SOXB1 Transcription Factors / antagonists & inhibitors*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology*
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Phytogenic
  • Drugs, Chinese Herbal
  • Jiedu Xiaozheng Yin
  • SOX2 protein, human
  • SOXB1 Transcription Factors