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Pitavastatin Induces Apoptosis of Cutaneous Squamous Cell Carcinoma Cells through Geranylgeranyl

Kyung-Il Kim1,2,3, Seung-Mee Kim1, Young-Yoon Lee1

  • 1Department of Dermatology, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon, Korea.

Annals of Dermatology
|April 12, 2023
PubMed
Abstract

Insights

Pitavastatin induces apoptosis in cutaneous squamous cell carcinoma (SCC) cells by activating c-Jun N-terminal kinase (JNK) signaling, a process dependent on geranylgeranyl pyrophosphate (GGPP). This targeted effect on cancer cells spares normal keratinocytes.

Area of Science:

  • Oncology
  • Pharmacology
  • Biochemistry

Background:

  • Pitavastatin is a widely used cholesterol-lowering drug.
  • Pitavastatin exhibits potential to induce apoptosis in cutaneous squamous cell carcinoma (SCC) cells.

Purpose of the Study:

  • To investigate the effects of pitavastatin on SCC cells.
  • To elucidate the underlying mechanisms of pitavastatin-induced apoptosis.

Main Methods:

  • Treatment of SCC cells (SCC12 and SCC13) with pitavastatin.
  • Confirmation of apoptosis induction via Western blot.
  • Supplementation studies with mevalonate, squalene, geranylgeranyl pyrophosphate (GGPP), and dolichol to assess pathway involvement.

Main Results:

  • Pitavastatin induced dose-dependent apoptosis in SCC cells without affecting normal keratinocytes.
  • Apoptosis was inhibited by mevalonate or GGPP supplementation, indicating a link to cholesterol synthesis intermediates.
  • Pitavastatin modulated intracellular signaling, decreasing specific regulators and increasing Rac1 and JNK activity, effects reversed by mevalonate or GGPP.

Conclusions:

  • Pitavastatin induces apoptosis in cutaneous SCC cells.
  • The mechanism involves GGPP-dependent activation of c-Jun N-terminal kinase (JNK).
  • JNK inhibition abrogated pitavastatin-induced apoptosis in SCC cells.
Keywords:
ApoptosisPitavastatinSquamous cell carcinoma cellsc-Jun N-terminal kinase

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