HDAC6-selective inhibitors enhance anticancer effects of paclitaxel in ovarian cancer cells

Yoo,Jung; Jeon,Yu Hyun; Lee,Dong Hoon; Kim,Go Woon; Lee,Sang Wu; Kim,So Yeon; Park,Jongsun; Kwon,So Hee

doi:10.3892/ol.2021.12462

HDAC6-selective inhibitors enhance anticancer effects of paclitaxel in ovarian cancer cells

Authors:
- Jung Yoo
- Yu Hyun Jeon
- Dong Hoon Lee
- Go Woon Kim
- Sang Wu Lee
- So Yeon Kim
- Jongsun Park
- So Hee Kwon
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Affiliations: Department of Pharmacy, College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 21983, Republic of Korea, Department of Pharmacology, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea
Published online on: January 12, 2021 https://doi.org/10.3892/ol.2021.12462
Article Number: 201

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Abstract

Histone deacetylase 6 (HDAC6)‑selective inhibitors are potent anticancer agents that are gaining increasing attention and undergoing various developments. These have been approved or are under clinical trials for use with other anticancer agents, such as pomalidomide, anti‑programmed death‑ligand 1 antibody and paclitaxel, for various types of cancer, including solid tumors. In the present study, a second generation HDAC6‑selective inhibitor, ACY‑241 (citarinostat), and a novel inhibitor, A452, exhibited synergistic anticancer effects with paclitaxel in AT‑rich interaction domain 1A‑mutated ovarian cancer in vitro. Co‑treatment of paclitaxel and the two HDAC6 inhibitors synergistically decreased cell growth and viability of TOV‑21G. Furthermore, the protein expression levels of pro‑apoptotic markers, such as poly(ADP‑ribose) polymerase, cleaved caspase‑3, Bak and Bax, were increased, whereas the expression levels of anti‑apoptotic markers, such as Bcl‑xL and Bcl‑2, were decreased synergistically. Treatment with all drug combinations increased the portion of apoptotic cells in fluorescence‑activated cell sorting analysis. These results demonstrated synergy between paclitaxel and HDAC6‑selective inhibitors, providing further impetus for clinical trials of combination therapy using HDAC6‑selective inhibitors, not only in ovarian cancer but also in other tumors.

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