PURPOSE: New treatment options for gastric cancer are in great demand. Histone deacetylases (HDACs) are exciting therapeutic targets, but only the class I HDACs 1, 2, and 3 have been studied in gastric cancer. We have investigated class IIa HDAC expression and inhibition in gastric cancer cells. EXPERIMENTAL DESIGN: We measured the level of 27 (phospho)proteins related to class IIa HDAC expression and function in ten laser-capture microdissection gastric tumor samples compared to patient-matched adjacent normal mucosa. Following, we evaluated class IIa HDAC inhibition by MC1568 in SNU-16 gastric cancer cells alone and in combination with cisplatin or docetaxel. RESULTS: We demonstrate for the first time an increase of HDAC4 in gastric tumor cells. HDAC4 inhibition had a synergistic effect with docetaxel treatment, shifting the cellular response from a cytostatic to a cytotoxic phenotype. This effect was associated with increased levels of cleaved caspases 3 and 9 and increased acetylated histone H3 Lys9/Lys14. CONCLUSIONS AND CLINICAL RELEVANCE: These data support in vivo studies investigating the potential clinical use of HDAC4 inhibitors in combination with docetaxel for the treatment of gastric cancer, lowering treatment doses of docetaxel to reduce the burden of adverse side effects on patients.
PURPOSE: New treatment options for gastric cancer are in great demand. Histone deacetylases (HDACs) are exciting therapeutic targets, but only the class I HDACs 1, 2, and 3 have been studied in gastric cancer. We have investigated class IIa HDAC expression and inhibition in gastric cancer cells. EXPERIMENTAL DESIGN: We measured the level of 27 (phospho)proteins related to class IIa HDAC expression and function in ten laser-capture microdissection gastric tumor samples compared to patient-matched adjacent normal mucosa. Following, we evaluated class IIa HDAC inhibition by MC1568 in SNU-16 gastric cancer cells alone and in combination with cisplatin or docetaxel. RESULTS: We demonstrate for the first time an increase of HDAC4 in gastric tumor cells. HDAC4 inhibition had a synergistic effect with docetaxel treatment, shifting the cellular response from a cytostatic to a cytotoxic phenotype. This effect was associated with increased levels of cleaved caspases 3 and 9 and increased acetylated histone H3 Lys9/Lys14. CONCLUSIONS AND CLINICAL RELEVANCE: These data support in vivo studies investigating the potential clinical use of HDAC4 inhibitors in combination with docetaxel for the treatment of gastric cancer, lowering treatment doses of docetaxel to reduce the burden of adverse side effects on patients.
Authors: Yanning Ma; Yongfang Yue; Min Pan; Jie Sun; Jue Chu; Xiaoying Lin; Wenxia Xu; Lifeng Feng; Yan Chen; Dingwei Chen; Vivian Y Shin; Xian Wang; Hongchuan Jin Journal: Am J Cancer Res Date: 2015-01-15 Impact factor: 6.166
Authors: Jiajun Luo; Hang Li; Nicole C Deziel; Huang Huang; Nan Zhao; Shuangge Ma; Xin Ni; Robert Udelsman; Yawei Zhang Journal: Environ Res Date: 2019-12-06 Impact factor: 6.498
Authors: Aamir Ahmad; Kevin R Ginnebaugh; Shuping Yin; Aliccia Bollig-Fischer; Kaladhar B Reddy; Fazlul H Sarkar Journal: BMC Cancer Date: 2015-07-24 Impact factor: 4.430