2. Academic Validation
  3. T52 attenuates oncogenic STAT3 signaling and suppresses osteosarcoma

T52 attenuates oncogenic STAT3 signaling and suppresses osteosarcoma

  • Phytomedicine. 2023 Jun:114:154799. doi: 10.1016/j.phymed.2023.154799.
Liru Tian 1,  Chuan Li 1,  Limin Xiang 2,  Jia Zeng 2,  Shuqing Chen 3,  Weimin Guo 4,  Shulin Chen 5,  Yihai Wang 2,  Xiangjiu He 6,  Peiqiang Su 7,  Caixia Xu 8
Affiliations

Affiliations

  • 1 Research Center for Translational Medicine, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510006, China.
  • 2 School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China; Guangdong Engineering Research Center for Lead Compounds & Drug Discovery, Guangzhou 510006, China.
  • 3 Department of Traditional Chinese Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510006, China.
  • 4 Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Department of Spine Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
  • 5 Research Center for Translational Medicine, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510006, China; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
  • 6 School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China; Guangdong Engineering Research Center for Lead Compounds & Drug Discovery, Guangzhou 510006, China. Electronic address: [email protected].
  • 7 Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Department of Spine Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; The Department of Orthopedics, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China. Electronic address: [email protected].
  • 8 Research Center for Translational Medicine, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510006, China. Electronic address: [email protected].
PMID: 37058945 DOI: 10.1016/j.phymed.2023.154799
Abstract

Background: T52 is a steroidal saponin extracted from the traditional Chinese herb Rohdea fargesii (Baill.), and it is reported to possess strong anti-proliferative capabilities in human pharyngeal carcinoma cell lines. However, whether T52 has anti-osteosarcoma properties, and its potential mechanism is remains unknown.

Purpose: To examine the outcome and underlying mechanism of T52 in osteosarcomas (OS).

Methods/study designs: The physiological roles of T52 in OS cells were examined using CCK-8, colony formation (CF), EdU staining, cell cycle/Apoptosis and cell migration/invasion assays. The relevant T52 targets against OS were assessed via bioinformatics prediction, and the binding sites were analyzed by molecular docking. Western blot analysis was carried out to examine the levels of factors associated with Apoptosis, cell cycle, and STAT3 signaling pathway activation.

Results: T52 markedly diminished the proliferation, migration, and invasion of OS cells, and promoted G2/M arrest and Apoptosis in a dose-dependent fashion (DDF) in vitro. Mechanistically, molecular docking predicted that T52 stably associated with STAT3 Src homology 2 (SH2) domain residues. Western blot revealed that T52 suppressed the STAT3 signaling pathway, as well as the expression of the downstream targets, such as, Bcl-2, Cyclin D1, and c-Myc. In addition, the anti-OS property of T52 were partially reversed by STAT3 reactivation, which confirmed that STAT3 signaling is critical for regulating the anti-OS property of T52.

Conclusion: We firstly demonstrated that T52 possessed strong anti-osteosarcoma property in vitro, which was brought on by the inhibition of the STAT3 signaling pathway. Our findings provided pharmacological support for treating OS with T52.

Keywords

Metastasis; Osteosarcoma; Proliferation; Rohdea fargesii; STAT3.

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