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Int J Mol Sci. 2019 Nov 29;20(23). pii: E6026. doi: 10.3390/ijms20236026.

A Small Compound KJ-28d Enhances the Sensitivity of Non-Small Cell Lung Cancer to Radio- and Chemotherapy.

Author information

1
Division of Radiation Biomedical Research, Korea Institute of Radiological & Medical Sciences (KIRAMS), Seoul 01812, Korea.
2
Department of Biology, Korea University, Seoul 02841, Korea.
3
Department of Medicinal Chemistry, Jungwon University, Goesan 28024, Korea.

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.

KEYWORDS:

DNA damage; chemotherapy; combination therapy; non-small cell lung cancer; poly (ADP-ribose) polymerase inhibitor; radiotherapy

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