Betulinic Acid Inhibits the Stemness of Gastric Cancer Cells by Regulating the GRP78-TGF-β1 Signaling Pathway and Macrophage Polarization.
Jen-Lung ChenYun-Shen TaiHsin-Yi TsaiChia-Yuan HsiehChun-Lin ChenChung-Jung LiuDeng-Chyang WuYaw-Bin HuangMing-Wei LinPublished in: Molecules (Basel, Switzerland) (2023)
Cancer stemness is the process by which cancer cells acquire chemoresistance and self-renewal in the tumor microenvironment. Glucose-regulated protein 78 (GRP78) is a biomarker for gastric cancer and is involved in cancer stemness. By inducing cancer stemness in various types of cancer, the polarization of macrophages into tumor-associated macrophages (TAMs) controls tumor progression. Betulinic acid (BA) is a bioactive natural compound with anticancer properties. However, whether GRP78 regulates TAM-mediated cancer stemness in the tumor microenvironment and whether BA inhibits GRP78-mediated cancer stemness in gastric cancer remain unknown. In this study, we investigated the role of GRP78 in gastric cancer stemness in a tumor microenvironment regulated by BA. The results indicated that BA inhibited not only GRP78-mediated stemness-related protein expression and GRP78-TGF-β-mediated macrophage polarization into TAMs, but also TAM-mediated cancer stemness. Therefore, BA is a promising candidate for clinical application in combination-chemotherapy targeting cancer stemness.
Keyphrases
- papillary thyroid
- stem cells
- epithelial mesenchymal transition
- squamous cell
- signaling pathway
- endoplasmic reticulum stress
- lymph node metastasis
- childhood cancer
- cancer stem cells
- oxidative stress
- transforming growth factor
- transcription factor
- blood pressure
- poor prognosis
- small molecule
- long non coding rna
- induced apoptosis
- binding protein