HDAC1 and HDAC2 double knockout triggers cell apoptosis in advanced thyroid cancer

Ching Ling Lin, Ming Lin Tsai, Chun Yu Lin, Kai Wen Hsu, Wen Shyang Hsieh, Wei Ming Chi, Li Chi Huang, Chia Hwa Lee

研究成果: 雜誌貢獻文章

1 引文 (Scopus)

摘要

Anaplastic thyroid carcinoma (ATC) and squamous thyroid carcinoma (STC) are both rare and advanced thyroid malignancies with a very poor prognosis and an average median survival time of 5 months and less than 20% of affected patients are alive 1 year after diagnosis. The clinical management of both ATC and STC is very similar because they are not particularly responsive to radiotherapy and chemotherapy. This inspired us to explore a novel and effective clinically approved therapy for ATC treatment. Histone deacetylase inhibitor (HDACi) drugs are recently FDA-approved drug for malignancies, especially for blood cell cancers. Therefore, we investigated whether an HDACi drug acts as an effective anticancer drug for advanced thyroid cancers. Cell viability analysis of panobinostat treatment demonstrated a significant IC50 of 0.075 µM on SW579 STC cells. In addition, panobinostat exposure activated histone acetylation and triggered cell death mainly through cell cycle arrest and apoptosis-related protein activation. Using CRISPR/Cas9 to knock out HDAC1 and HDAC2 genes in SW579 cells, we observed that the histone acetylation level and cell cycle arrest were enhanced without any impact on cell growth. Furthermore, HDAC1 and HDAC2 double knockout (KO) cells showed dramatic cell apoptosis activation compared to HDAC1 and HDAC2 individual KO cells. This suggests expressional and biofunctional compensation between HDAC1 and HDAC2 on SW579 cells. This study provides strong evidence that panobinostat can potentially be used in the clinic of advanced thyroid cancer patients.
原文英語
文章編號454
期刊International Journal of Molecular Sciences
20
發行號2
DOIs
出版狀態已發佈 - 一月 2 2019

指紋

apoptosis
Cell death
Thyroid Neoplasms
actuators
cancer
Cells
Apoptosis
Acetylation
Histone Deacetylase Inhibitors
cells
Pharmaceutical Preparations
Histones
Clustered Regularly Interspaced Short Palindromic Repeats
Chemical activation
Squamous Cell Carcinoma
drugs
acetylation
Chemotherapy
Cell Cycle Checkpoints
Radiotherapy

ASJC Scopus subject areas

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

引用此文

HDAC1 and HDAC2 double knockout triggers cell apoptosis in advanced thyroid cancer. / Lin, Ching Ling; Tsai, Ming Lin; Lin, Chun Yu; Hsu, Kai Wen; Hsieh, Wen Shyang; Chi, Wei Ming; Huang, Li Chi; Lee, Chia Hwa.

於: International Journal of Molecular Sciences, 卷 20, 編號 2, 454, 02.01.2019.

研究成果: 雜誌貢獻文章

Lin, Ching Ling ; Tsai, Ming Lin ; Lin, Chun Yu ; Hsu, Kai Wen ; Hsieh, Wen Shyang ; Chi, Wei Ming ; Huang, Li Chi ; Lee, Chia Hwa. / HDAC1 and HDAC2 double knockout triggers cell apoptosis in advanced thyroid cancer. 於: International Journal of Molecular Sciences. 2019 ; 卷 20, 編號 2.
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abstract = "Anaplastic thyroid carcinoma (ATC) and squamous thyroid carcinoma (STC) are both rare and advanced thyroid malignancies with a very poor prognosis and an average median survival time of 5 months and less than 20{\%} of affected patients are alive 1 year after diagnosis. The clinical management of both ATC and STC is very similar because they are not particularly responsive to radiotherapy and chemotherapy. This inspired us to explore a novel and effective clinically approved therapy for ATC treatment. Histone deacetylase inhibitor (HDACi) drugs are recently FDA-approved drug for malignancies, especially for blood cell cancers. Therefore, we investigated whether an HDACi drug acts as an effective anticancer drug for advanced thyroid cancers. Cell viability analysis of panobinostat treatment demonstrated a significant IC50 of 0.075 µM on SW579 STC cells. In addition, panobinostat exposure activated histone acetylation and triggered cell death mainly through cell cycle arrest and apoptosis-related protein activation. Using CRISPR/Cas9 to knock out HDAC1 and HDAC2 genes in SW579 cells, we observed that the histone acetylation level and cell cycle arrest were enhanced without any impact on cell growth. Furthermore, HDAC1 and HDAC2 double knockout (KO) cells showed dramatic cell apoptosis activation compared to HDAC1 and HDAC2 individual KO cells. This suggests expressional and biofunctional compensation between HDAC1 and HDAC2 on SW579 cells. This study provides strong evidence that panobinostat can potentially be used in the clinic of advanced thyroid cancer patients.",
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AU - Chi, Wei Ming

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AU - Lee, Chia Hwa

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AB - Anaplastic thyroid carcinoma (ATC) and squamous thyroid carcinoma (STC) are both rare and advanced thyroid malignancies with a very poor prognosis and an average median survival time of 5 months and less than 20% of affected patients are alive 1 year after diagnosis. The clinical management of both ATC and STC is very similar because they are not particularly responsive to radiotherapy and chemotherapy. This inspired us to explore a novel and effective clinically approved therapy for ATC treatment. Histone deacetylase inhibitor (HDACi) drugs are recently FDA-approved drug for malignancies, especially for blood cell cancers. Therefore, we investigated whether an HDACi drug acts as an effective anticancer drug for advanced thyroid cancers. Cell viability analysis of panobinostat treatment demonstrated a significant IC50 of 0.075 µM on SW579 STC cells. In addition, panobinostat exposure activated histone acetylation and triggered cell death mainly through cell cycle arrest and apoptosis-related protein activation. Using CRISPR/Cas9 to knock out HDAC1 and HDAC2 genes in SW579 cells, we observed that the histone acetylation level and cell cycle arrest were enhanced without any impact on cell growth. Furthermore, HDAC1 and HDAC2 double knockout (KO) cells showed dramatic cell apoptosis activation compared to HDAC1 and HDAC2 individual KO cells. This suggests expressional and biofunctional compensation between HDAC1 and HDAC2 on SW579 cells. This study provides strong evidence that panobinostat can potentially be used in the clinic of advanced thyroid cancer patients.

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