Bibliographic Details
| Title: |
Downregulation of Mcl-1 by Panobinostat Potentiates Proton Beam Therapy in Hepatocellular Carcinoma Cells |
| Authors: |
Changhoon Choi, Ga Haeng Lee, Arang Son, Gyu Sang Yoo, Jeong Il Yu, Hee Chul Park |
| Source: |
Cells, Vol 10, Iss 3, p 554 (2021) |
| Publisher Information: |
MDPI AG, 2021. |
| Publication Year: |
2021 |
| Collection: |
LCC:Cytology |
| Subject Terms: |
proton therapy, hepatocellular carcinoma, panobinostat, Mcl-1, Cytology, QH573-671 |
| More Details: |
Epigenetic modulation by histone deacetylase (HDAC) inhibitors is an attractive anti-cancer strategy for diverse hematological and solid cancers. Herein, we explored the relative effectiveness of the pan-HDAC inhibitor panobinostat in combination with proton over X-ray irradiation in HCC cells. Clonogenic survival assays revealed that radiosensitization of Huh7 and Hep3B cells by panobinostat was more evident when combined with protons than X-rays. Panobinostat increased G2/M arrest and production of intracellular reactive oxygen species, which was further enhanced by proton irradiation. Immunofluorescence staining of γH2AX showed that panobinostat enhanced proton-induced DNA damage. Panobinostat dose-dependently decreased expression of an anti-apoptotic protein, Mcl-1, concomitant with increasing acetylation of histone H4. The combination of panobinostat with proton irradiation enhanced apoptotic cell death to a greater extent than that with X-ray irradiation. Depletion of Mcl-1 by RNA interference enhanced proton-induced apoptosis and proton radiosensitization, suggesting a potential role of Mcl-1 in determining proton sensitivity. Together, our findings suggest that panobinostat may be a promising combination agent for proton beam therapy in HCC treatment. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2073-4409 |
| Relation: |
https://www.mdpi.com/2073-4409/10/3/554; https://doaj.org/toc/2073-4409 |
| DOI: |
10.3390/cells10030554 |
| Access URL: |
https://doaj.org/article/fbf59fefad6d48dfa68922506fc6f2f4 |
| Accession Number: |
edsdoj.fbf59fefad6d48dfa68922506fc6f2f4 |
| Database: |
Directory of Open Access Journals |
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