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Gossypetin Inhibits Solar-UV Induced Cutaneous Basal Cell Carcinoma Through Direct Inhibiting PBK/TOPK Protein Kinase

Lijuan Wang1, Zixi Zhang1, Rui Ge1

  • 1Department of Dermatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.

Anti-Cancer Agents in Medicinal Chemistry
|March 5, 2019
PubMed
Abstract

Insights

Gossypetin effectively inhibits PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) activity, thereby alleviating solar UV-induced skin cancer. This natural compound shows promise as a therapeutic agent for preventing and treating cutaneous basal cell carcinoma.

Area of Science:

  • Dermatology and Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Excessive solar UV exposure is linked to skin photoaging, inflammation, and cancer.
  • PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) regulates key signaling pathways (p38 MAPK, ERK1/2) involved in skin cancer development.
  • PBK/TOPK is a significant factor in solar UV-induced cutaneous basal cell carcinoma (BCC), suggesting it as a therapeutic target.

Purpose of the Study:

  • To investigate the role of PBK/TOPK in human cutaneous BCC.
  • To evaluate the potential of Gossypetin as an agent to target PBK/TOPK and mitigate solar UV-induced skin damage.
  • To determine the interaction between Gossypetin and PBK/TOPK and its effect on signaling pathways.

Main Methods:

  • Analysis of PBK/TOPK expression in human BCC tissues.
  • Ex vivo demonstration of solar UV-induced p38 MAPK and ERK1/2 phosphorylation.
  • In vitro kinase and Microscale Thermophoresis (MST) assays to detect Gossypetin-PBK/TOPK interaction.
  • Ex vivo and in vivo studies to assess Gossypetin's effect on PBK/TOPK activity and UV-induced signaling.

Main Results:

  • PBK/TOPK, phosphor-p38 MAPK, and phosphor-ERK1/2 were upregulated in human BCC tissues.
  • Solar UV treatment increased phosphor-p38 MAPK and phosphor-ERK1/2 in HaCaT cells.
  • Gossypetin bound to PBK/TOPK, suppressed its activity, and inhibited UV-induced phosphorylation of PBK/TOPK, p38 MAPK, ERK1/2, and H2AX in cells and mice.
  • Gossypetin exhibited no cytotoxicity in HaCaT cells.

Conclusions:

  • Gossypetin effectively inhibits solar UV-induced cutaneous basal cell carcinoma by targeting PBK/TOPK.
  • Gossypetin demonstrates significant potential as a therapeutic agent for preventing and treating solar UV-induced skin cancer.
  • Blocking PBK/TOPK activity with Gossypetin offers a promising strategy against UV-induced skin damage and BCC development.
Keywords:
GossypetinMAPKPBK/TOPKcutaneous basal cell carcinomamicroscale thermophoresis assaysolar-UV.

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