Simvastatin inhibits cell proliferation and migration in human anaplastic thyroid cancer

Mei Chieh Chen, Yuan Chin Tsai, Jen Ho Tseng, Jr Jiun Liou, Steve Horng, Heng Ching Wen, Yu Ching Fan, Wen Bin Zhong, Sung Po Hsu

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Malignant human anaplastic thyroid cancer (ATC) is pertinacious to conventional therapies. The present study investigated the anti-cancer activity of simvastatin and its underlying regulatory mechanism in cultured ATC cells. Simvastatin (0-20 µM) concentration-dependently reduced cell viability and relative colony formation. Depletions of mevalonate (MEV) and geranylgeranyl pyrophosphate (GGpp) by simvastatin induced G1 arrest and increased apoptotic cell populations at the sub-G1 phase. Adding MEV and GGpp prevented the simvastatin-inhibited cell proliferation. Immunoblotting analysis illustrated that simvastatin diminished the activation of RhoA and Rac1 protein, and this effect was prevented by pre-treatment with MEV and GGpp. Simvastatin increased the levels of p21cip and p27kip proteins and reduced the levels of hyperphosphorylated-Rb, E2F1 and CCND1 proteins. Adding GGpp abolished the simvastatin-increased levels of p27kip protein, and the GGpp-caused effect was abolished by Skp2 inhibition. Introduction of Cyr61 siRNA into ATC cells prevented the epidermal growth factor (EGF)-enhanced cell migration. The EGF-induced increases of Cyr61 protein expression and cell migration were prevented by simvastatin. Taken together, these results suggest that simvastatin induced ATC proliferation inhibition through the deactivation of RhoA/Rac1 protein and overexpression of p21cip and p27kip, and migration inhibition through the abrogation of Cyr61 protein expression.

Original languageEnglish
Article number2690
JournalInternational Journal of Molecular Sciences
Volume18
Issue number12
DOIs
Publication statusPublished - Dec 13 2017

Fingerprint

Simvastatin
Cell proliferation
Cell Movement
cancer
Cell Proliferation
proteins
Proteins
rac1 GTP-Binding Protein
rhoA GTP-Binding Protein
cells
Epidermal Growth Factor
Cells
Anaplastic Thyroid Carcinoma
viability
Retinoblastoma Protein
pretreatment
deactivation
Cyclin D1
G1 Phase
therapy

Keywords

  • Anaplastic thyroid cancer
  • p21
  • p27
  • RhoA
  • Simvastatin

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Simvastatin inhibits cell proliferation and migration in human anaplastic thyroid cancer. / Chen, Mei Chieh; Tsai, Yuan Chin; Tseng, Jen Ho; Liou, Jr Jiun; Horng, Steve; Wen, Heng Ching; Fan, Yu Ching; Zhong, Wen Bin; Hsu, Sung Po.

In: International Journal of Molecular Sciences, Vol. 18, No. 12, 2690, 13.12.2017.

Research output: Contribution to journalArticle

Chen, Mei Chieh ; Tsai, Yuan Chin ; Tseng, Jen Ho ; Liou, Jr Jiun ; Horng, Steve ; Wen, Heng Ching ; Fan, Yu Ching ; Zhong, Wen Bin ; Hsu, Sung Po. / Simvastatin inhibits cell proliferation and migration in human anaplastic thyroid cancer. In: International Journal of Molecular Sciences. 2017 ; Vol. 18, No. 12.
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