2. Academic Validation
  3. Rhodiolin inhibits the PI3K/AKT/mTOR signaling pathway via the glycolytic enzyme GPI in human papillary thyroid cancer

Rhodiolin inhibits the PI3K/AKT/mTOR signaling pathway via the glycolytic enzyme GPI in human papillary thyroid cancer

  • Phytomedicine. 2024 Jun 25:132:155804. doi: 10.1016/j.phymed.2024.155804.
Jiaqiang Bo 1,  Shuyu Mao 1,  Jie Yang 1,  Li Wang 1,  Jia Zheng 1,  Chunyu Zhang 1,  Mingming Song 2,  Siyu Chen 3,  Chang Liu 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing, China; School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
  • 2 State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing, China; School of Life Science and Technology, China Pharmaceutical University, Nanjing, China. Electronic address: 1520210049@cpu.edu.cn.
  • 3 State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing, China; School of Life Science and Technology, China Pharmaceutical University, Nanjing, China. Electronic address: siyuchen@cpu.edu.cn.
  • 4 State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing, China; School of Life Science and Technology, China Pharmaceutical University, Nanjing, China; Department of Endocrinology, Nanjing Drum Tower Hospital, School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China. Electronic address: changliu@cpu.edu.cn.
PMID: 38943696 DOI: 10.1016/j.phymed.2024.155804
Abstract

Background: Papillary thyroid carcinoma (PTC) is an endocrine malignant tumor of the head and neck. Surgery and chemotherapy are PTC treatments, but have adverse effects. Exploration of new non-toxic anti-PTC drugs for PTC treatment is an unmet need.

Methods: We aimed to identify anti-PTC drugs that could inhibit PTC-cell proliferation through high-throughput screening of a library of well-characterized naturally occurring small-molecule compounds. Then, the anti-PTC function of rhodiolin was validated by in vitro cell models and xenograft tumor models RESULTS: We initially demonstrated that rhodiolin inhibited the growth and induced the Apoptosis of PTC cells significantly in vitro and in vivo. At the metabolic level, rhodiolin blocked glycolysis through glucose 6-phosphate isomerase (GPI), which suggested that glycolytic inhibition may be involved in mediating the anti-PTC function of rhodiolin. Transcriptomics analysis combined with bioinformatics analysis identified rhodiolin treatment to inhibit phosphorylation of the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway. Collectively, our findings demonstrated that rhodiolin inhibited the proliferation and induced the Apoptosis of PTC cells by blocking glycolysis through the glycolytic Enzyme GPI, thereby inhibiting phosphorylation of the PI3K/Akt/mTOR signaling pathway.

Conclusion: Our study demonstrates the potential use of rhodiolin in inhibiting the proliferation and inducing the Apoptosis of PTC cells. Inhibition of phosphorylation of the PI3K/Akt/mTOR signaling pathway mediated by GPI plays an extremely important part in the ant-PTC function of rhodiolin. These results suggest that rhodiolin is a promising drug in the treatment of PTC progression. Our results provide a novel target and cell signaling pathway for PTC therapy from the perspective of energy metabolism, which could provide new perspectives and new drug choices for PTC therapy. In addition to that, our study will help to make up for the lack of drug research for PTC.

Keywords

Glucose 6-phosphate isomerase; Glycolysis; Papillary thyroid cancer; Rhodiolin.

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