Isoliquiritigenin Inhibits Gastric Cancer Stemness, Modulates Tumor Microenvironment, and Suppresses Tumor Growth through Glucose-Regulated Protein 78 Downregulation.
Chien-Hsing LeeHsin-Yi TsaiChun-Lin ChenJen-Lung ChenChao-Chun LuYi-Ping FangDeng-Chyang WuYaw-Bin HuangMing-Wei LinPublished in: Biomedicines (2022)
Chemotherapy is the treatment of choice for gastric cancer; however, the currently available therapeutic drugs for treatment have limited efficacy. Cancer stemness and the tumor microenvironment may play crucial roles in tumor growth and chemoresistance. Glucose-regulated protein 78 (GRP78) is an endoplasmic reticulum chaperone facilitating protein folding and cell homeostasis during stress and may participate in chemoresistance. Isoliquiritigenin (ISL) is a bioactive flavonoid found in licorice. In this study, we demonstrated the role of GRP78 in gastric cancer stemness and evaluated GRP78-mediated stemness inhibition, tumor microenvironment regulation, and chemosensitivity promotion by ISL. ISL not only suppressed GRP78-mediated gastric cancer stem cell-like characteristics, stemness-related protein expression, and cancer-associated fibroblast activation but also gastric tumor growth in xenograft animal studies. The findings indicated that ISL is a promising candidate for clinical use in combination chemotherapy.
Keyphrases
- cancer stem cells
- stem cells
- epithelial mesenchymal transition
- endoplasmic reticulum
- endoplasmic reticulum stress
- protein protein
- transcription factor
- cell surface
- signaling pathway
- single cell
- binding protein
- type diabetes
- cell proliferation
- squamous cell carcinoma
- locally advanced
- mesenchymal stem cells
- skeletal muscle
- drug induced
- rectal cancer
- smoking cessation