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.
Original language | English |
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Article number | 6026 |
Journal | International journal of molecular sciences |
Volume | 20 |
Issue number | 23 |
DOIs | |
Publication status | Published - 2019 Dec 1 |
Bibliographical note
Funding Information:Funding: This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2016R1D1A1B03936420; NRF-2016R1D1A3B03935674), and the Korea Institute of Radiological and Medical Sciences funded by the Ministry of Science and ICT, Republic of Korea (50531-2019; 50538-2019).
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
Keywords
- Chemotherapy
- Combination therapy
- DNA damage
- Non-small cell lung cancer
- Poly (ADP-ribose) polymerase inhibitor
- Radiotherapy
ASJC Scopus subject areas
- Catalysis
- Molecular Biology
- Spectroscopy
- Computer Science Applications
- Physical and Theoretical Chemistry
- Organic Chemistry
- Inorganic Chemistry