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Open AccessArticle

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

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
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(23), 6026; https://doi.org/10.3390/ijms20236026
Received: 10 October 2019 / Revised: 22 November 2019 / Accepted: 29 November 2019 / Published: 29 November 2019
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. View Full-Text
Keywords: poly (ADP-ribose) polymerase inhibitor; non-small cell lung cancer; DNA damage; radiotherapy; chemotherapy; combination therapy poly (ADP-ribose) polymerase inhibitor; non-small cell lung cancer; DNA damage; radiotherapy; chemotherapy; combination therapy
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Ryu, H.; Kim, H.J.; Song, J.-Y.; Hwang, S.-G.; Kim, J.-S.; Kim, J.; Bui, T.H.N.; Choi, H.-K.; Ahn, J. A Small Compound KJ-28d Enhances the Sensitivity of Non-Small Cell Lung Cancer to Radio- and Chemotherapy. Int. J. Mol. Sci. 2019, 20, 6026.

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