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DCLK1 might be a therapeutic target of osthole against cervical cancer

Liuliu Pan1, Xiaodan Zhang2, Danhan Wang1

  • 1Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Die Pharmazie
|October 8, 2021
PubMed

Insights

Osthole effectively induces apoptosis in cervical cancer cells. This natural compound likely targets DCLK1, offering a potential new therapeutic strategy for cervical cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Precise treatment of cervical cancer requires identifying effective compounds and their molecular targets.
  • Osthole is a natural compound with potential anti-cancer properties.

Purpose of the Study:

  • To investigate the anti-cervical cancer effects of osthole.
  • To explore Doublecortin-Like Kinase 1 (DCLK1) as a potential molecular target for osthole.

Main Methods:

  • Cell apoptosis was assessed using Annexin V-PE staining and flow cytometry.
  • Apoptosis-related biomarkers were analyzed via immunoblotting.
  • Cell proliferation was evaluated using MTT assays, molecular docking, and analysis of clinical data from cBioPortal.

Main Results:

  • Osthole significantly induced apoptosis in HeLa and Me-180 cervical cancer cell lines.
  • Osthole's anti-proliferative effect was antagonized by a DCLK1 inhibitor, suggesting competitive binding.
  • Molecular docking revealed osthole interacts with Val468 residues of DCLK1 via hydrogen bonds.
  • DCLK1 is frequently altered in cervical cancer and associated with tumor survival and recurrence.

Conclusions:

  • Osthole exhibits significant anti-survival effects on cervical cancer cells.
  • Osthole likely targets DCLK1 mechanistically through interaction with Val468.
  • DCLK1 represents a promising therapeutic target for cervical cancer.

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