A Small Compound KJ-28d Enhances the Sensitivity of Non-Small Cell Lung Cancer to Radio- and Chemotherapy
- Authors
- Ryu, Hwani; Kim, Hyo Jeong; Song, Jie-Young; Hwang, Sang-Gu; Kim, Jae-Sung; Kim, Joon; Bui, Thi Hong Nhung; Choi, Hyun-Kyung; Ahn, Jiyeon
- Issue Date
- 12월-2019
- Publisher
- MDPI
- Keywords
- poly (ADP-ribose) polymerase inhibitor; non-small cell lung cancer; DNA damage; radiotherapy; chemotherapy; combination therapy
- Citation
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.20, no.23
- Indexed
- SCIE
SCOPUS
- Journal Title
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
- Volume
- 20
- Number
- 23
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/61376
- DOI
- 10.3390/ijms20236026
- ISSN
- 1661-6596
- Abstract
- We previously reported on a poly (ADP-ribose) polymerase (PARP) 1/2 inhibitor N-(3-(hydroxycarbamoyl)phenyl)carboxamide (designated KJ-28d), which increased the death of human ovarian cancer BRCA1-deficient SNU-251 cells. In the present study, we further investigated the antitumor activities of KJ-28d in BRCA-proficient non-small cell lung cancer (NSCLC) cells to expand the use of PARP inhibitors. KJ-28d significantly inhibited the growth of NSCLC cells in vitro and in vivo, and induced DNA damage and reactive oxygen species in A549 and H1299 cells. Combined treatment with KJ-28d and ionizing radiation led to increased DNA damage responses in A549 and H1299 cells compared to KJ-28d or ionizing radiation alone, resulting in apoptotic cell death. Moreover, the combination of KJ-28d plus a DNA-damaging therapeutic agent (carboplatin, cisplatin, paclitaxel, or doxorubicin) synergistically inhibited cell proliferation, compared to either drug alone. Taken together, the findings demonstrate the potential of KJ-28d as an effective anti-cancer therapeutic agent for BRCA-deficient and -proficient cancer cells. KJ-28d might have potential as an adjuvant when used in combination with radiotherapy or DNA-damaging agents, pending further investigations.
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Collections - Graduate School > Department of Life Sciences > 1. Journal Articles
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