Effect of Functional Inhibition of BACE1 on Sensitization to γ-Irradiation in Cancer Cells
| Title: | Effect of Functional Inhibition of BACE1 on Sensitization to γ-Irradiation in Cancer Cells |
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| Authors: | Keitaro Nakamoto, Sota Kikuhara, Hiroaki Fujimori, Barkha Saraswat, Zhongming Gao, Ankitha Vadi Velu, Zongxiang Zhang, Ying Tong, Shoji Imamichi, Tadashige Nozaki, Yasufumi Murakami, Mitsuko Masutani |
| Source: | Current Issues in Molecular Biology, Vol 46, Iss 1, Pp 450-460 (2024) |
| Publisher Information: | MDPI AG, 2024. |
| Publication Year: | 2024 |
| Collection: | LCC:Biology (General) |
| Subject Terms: | BACE1, γ-H2AX, γ-irradiation, radiosensitization, cancer cell, Biology (General), QH301-705.5 |
| More Details: | Developing strategies for the radiosensitization of cancer cells by the inhibition of genes, which harbor low toxicity to normal cells, will be useful for improving cancer radiotherapy. Here, we focused on a β-site of amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1; β-secretase, memapsin-2). By functional inhibition of this peptidase by siRNA, it has also recently been shown that the DNA strand break marker, γH2AX foci, increased, suggesting its involvement in DNA damage response. To investigate this possibility, we knocked down BACE1 with siRNA in cancer cell lines, and sensitization to γ-irradiation was examined by a colony formation assay, γH2AX foci and level analysis, and flow cytometry. BACE1 knockdown resulted in the sensitization of HeLa, MDA-MB-231, U2OS, and SAOS cells to γ-irradiation in a diverse range. BACE1 knockdown showed a weak radiosensitization effect in osteosarcoma U2OS cells, which has a normal p53 function. HeLa and SAOS cells, which harbor p53 dysfunction, exhibited a greater level of radiosensitization. These results suggest that BACE1 may be a potential target for the radiosensitization in particular cancer cells. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1467-3045 1467-3037 |
| Relation: | https://www.mdpi.com/1467-3045/46/1/28; https://doaj.org/toc/1467-3037; https://doaj.org/toc/1467-3045 |
| DOI: | 10.3390/cimb46010028 |
| Access URL: | https://doaj.org/article/6ed9f65723f547d58794e264974344c5 |
| Accession Number: | edsdoj.6ed9f65723f547d58794e264974344c5 |
| Database: | Directory of Open Access Journals |
| ISSN: | 14673045 14673037 |
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| DOI: | 10.3390/cimb46010028 |
| Published in: | Current Issues in Molecular Biology |
| Language: | English |