2. Academic Validation
  3. Oxypalmatine regulates proliferation and apoptosis of breast cancer cells by inhibiting PI3K/AKT signaling and its efficacy against breast cancer organoids

Oxypalmatine regulates proliferation and apoptosis of breast cancer cells by inhibiting PI3K/AKT signaling and its efficacy against breast cancer organoids

  • Phytomedicine. 2023 Jun:114:154752. doi: 10.1016/j.phymed.2023.154752.
Xian Lin 1,  Dong Chen 2,  Xinyu Chu 2,  Lianxiang Luo 3,  Zhihao Liu 4,  Jian Chen 5
Affiliations

Affiliations

  • 1 Peking University Shenzhen Hospital; Shenzhen Key Laboratory of Inflammatory and Immunology Diseases, Shenzhen 518036, Guangdong, China.
  • 2 Department of Thyroid and Breast Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong, China.
  • 3 The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, Guangdong, China.
  • 4 The First Clinical College, Guangdong Medical University, Zhanjiang 524023, Guangdong, China.
  • 5 Peking University Shenzhen Hospital; Shenzhen Key Laboratory of Inflammatory and Immunology Diseases, Shenzhen 518036, Guangdong, China. Electronic address: [email protected].
PMID: 36948141 DOI: 10.1016/j.phymed.2023.154752
Abstract

Background: Breast Cancer (BC) is known as the most common Cancer in women. Discovering novel and effective drugs is a priority for the treatment of BC. Oxypalmatine (OPT) is a natural protoberberine-type alkaloid isolated from Phellodendron amurense Rupr. (Rutaceae) with potential anti-cancer activity.

Purpose: This investigation aimed to elucidate the biological role and potential mechanisms of OPT in BC cells, and intended to assess the therapeutic potential of OPT in BC patient-derived Organoid models.

Methods: CCK-8 and EdU assays, and flow cytometry were used to test the activity of OPT against BC cells. In addition, patient-derived Organoid models were constructed to assess the therapeutic efficiency of OPT in BC. Besides, network pharmacological analysis and RNA Sequencing analysis were performed to predict the underlying anti-BC mechanism of OPT. Moreover, Western blot analysis was applied to test the expression of genes modulated by OPT.

Results: OPT attenuated the proliferation and DNA replication, and induced Apoptosis in multiple BC cells. Interestingly, OPT also exerted a cytotoxic effect on BC organoids characterized as luminal A, HER2-overexpressing, and triple-negative subtypes, indicating that OPT was a potential broad-spectrum Anticancer drug. Network pharmacological analysis suggested that OPT might affect signals contributing to BC progression, including PI3K/Akt, MAPK, and VEGFA-VEGFR2 signaling pathways. Moreover, bioinformatics analysis of data from our RNA Sequencing suggested that PI3K/Akt was a downstream pathway of OPT in BC. Finally, OPT was shown to inactivate PI3K/Akt signaling pathway in BC cells by Western blot analysis.

Conclusions: Collectively, our study demonstrated that OPT suppressed proliferation and induced Apoptosis through mitigating the PI3K/Akt signaling pathway in BC cells. Moreover, our work first adopted BC Organoid models to confirm OPT as an effective and promising drug, laying a foundation for the potential use of OPT in BC treatment.

Keywords

Bioinformatics; Breast cancer; Organoids; Oxypalmatine; PI3K/AKT.

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