Abstract
ACY-1215, also known as ricolinostat, is a leading histone deacetylase 6 inhibitor, which is currently being tested in clinical trials for hematological malignancies. Previous studies have reported that ACY-1215 is not potent enough as a monotherapy for the treatment of colorectal cancer (CRC), which generally requires combination therapy for successful treatment. Therefore, the present study aimed to determine whether the synergistic interaction detected between ACY-1215 and anticancer agents in hematological cancers could occur in solid tumors. The results of the present study indicated that ACY-1215 exerted a potent synergistic anti-proliferative effect when used in combination with anticancer agents in CRC cells. The combination of ACY-1215 and oxaliplatin was more potent than either drug alone, as indicated by an increase in apoptotic cells and their effects on the apoptotic pathway; ACY-1215 and oxaliplatin cotreatment activated caspase-3 and poly (ADP ribose) polymerase, increased B-cell lymphoma (Bcl)-2 homologous antagonist/killer expression, and decreased Bcl-extra large protein, phosphorylated-extracellular signal-regulated kinase and phosphorylated-protein kinase B expression. In addition, combined treatment of ACY-1215 and anticancer agents induced synergistic upregulation of programmed death-ligand 1. These findings suggested that a therapeutic strategy that combines ACY-1215 and oxaliplatin warrants attention for the treatment of solid tumors, including CRC.
| Original language | English |
|---|---|
| Pages (from-to) | 844-854 |
| Number of pages | 11 |
| Journal | International journal of oncology |
| Volume | 53 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2018 Aug 1 |
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All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
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The HDAC6 inhibitor ACY-1215 enhances the anticancer activity of oxaliplatin in colorectal cancer cells. / Lee, Dong Hoon; Won, Hye Rim; Ryu, Hyun Wook; Han, Jung Min; Kwon, So Hee.
In: International journal of oncology, Vol. 53, No. 2, 01.08.2018, p. 844-854.Research output: Contribution to journal › Article
TY - JOUR
T1 - The HDAC6 inhibitor ACY-1215 enhances the anticancer activity of oxaliplatin in colorectal cancer cells
AU - Lee, Dong Hoon
AU - Won, Hye Rim
AU - Ryu, Hyun Wook
AU - Han, Jung Min
AU - Kwon, So Hee
PY - 2018/8/1
Y1 - 2018/8/1
N2 - ACY-1215, also known as ricolinostat, is a leading histone deacetylase 6 inhibitor, which is currently being tested in clinical trials for hematological malignancies. Previous studies have reported that ACY-1215 is not potent enough as a monotherapy for the treatment of colorectal cancer (CRC), which generally requires combination therapy for successful treatment. Therefore, the present study aimed to determine whether the synergistic interaction detected between ACY-1215 and anticancer agents in hematological cancers could occur in solid tumors. The results of the present study indicated that ACY-1215 exerted a potent synergistic anti-proliferative effect when used in combination with anticancer agents in CRC cells. The combination of ACY-1215 and oxaliplatin was more potent than either drug alone, as indicated by an increase in apoptotic cells and their effects on the apoptotic pathway; ACY-1215 and oxaliplatin cotreatment activated caspase-3 and poly (ADP ribose) polymerase, increased B-cell lymphoma (Bcl)-2 homologous antagonist/killer expression, and decreased Bcl-extra large protein, phosphorylated-extracellular signal-regulated kinase and phosphorylated-protein kinase B expression. In addition, combined treatment of ACY-1215 and anticancer agents induced synergistic upregulation of programmed death-ligand 1. These findings suggested that a therapeutic strategy that combines ACY-1215 and oxaliplatin warrants attention for the treatment of solid tumors, including CRC.
AB - ACY-1215, also known as ricolinostat, is a leading histone deacetylase 6 inhibitor, which is currently being tested in clinical trials for hematological malignancies. Previous studies have reported that ACY-1215 is not potent enough as a monotherapy for the treatment of colorectal cancer (CRC), which generally requires combination therapy for successful treatment. Therefore, the present study aimed to determine whether the synergistic interaction detected between ACY-1215 and anticancer agents in hematological cancers could occur in solid tumors. The results of the present study indicated that ACY-1215 exerted a potent synergistic anti-proliferative effect when used in combination with anticancer agents in CRC cells. The combination of ACY-1215 and oxaliplatin was more potent than either drug alone, as indicated by an increase in apoptotic cells and their effects on the apoptotic pathway; ACY-1215 and oxaliplatin cotreatment activated caspase-3 and poly (ADP ribose) polymerase, increased B-cell lymphoma (Bcl)-2 homologous antagonist/killer expression, and decreased Bcl-extra large protein, phosphorylated-extracellular signal-regulated kinase and phosphorylated-protein kinase B expression. In addition, combined treatment of ACY-1215 and anticancer agents induced synergistic upregulation of programmed death-ligand 1. These findings suggested that a therapeutic strategy that combines ACY-1215 and oxaliplatin warrants attention for the treatment of solid tumors, including CRC.
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U2 - 10.3892/ijo.2018.4405
DO - 10.3892/ijo.2018.4405
M3 - Article
VL - 53
SP - 844
EP - 854
JO - International Journal of Oncology
JF - International Journal of Oncology
SN - 1019-6439
IS - 2
ER -